Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | ||||||
{[ item.p_purity ]} | {[ item.pr_size ]} | Inquiry |
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price) ]} |
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price) ]} | {[ item.pr_usastock ]} | in stock Inquiry - | {[ item.pr_chinastock ]} | {[ item.pr_remark ]} in stock Inquiry - | Login | Inquiry |
Please Login or Create an Account to: See VIP prices and availability
CAS No. : | 608141-43-1 | MDL No. : | MFCD28167941 |
Formula : | C20H34N2O7S | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | KJZXYHPZWRDLAR-JIJBYVMQSA-N |
M.W : | 446.56 | Pubchem ID : | 66648136 |
Synonyms : |
|
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In methanol; at 20℃; for 8h;Reflux; Resolution of racemate; | A 3 L 3-necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with 2-(3 -ethoxy-4-methoxyphenyl)- 1 -(methylsulphonyl)-eth-2-ylamine (137.0 g, 500 mmol), N-acetyl-L-leucine (52 g, 300 mmol), and methanol (1.0 L). The stirred slurry was heated to reflux for 1 hour. The stirred mixture was allowed to cool to ambient temperature and stirring was continued for another 3 hours at ambient temperature. The slurry was filtered andwashed with methanol (250 mL). The solid was air-dried and then dried in vacuo at ambient temperature to a constant weight, giving 109.5 g (98% yield) of the crude product (85.8% ee). The crude solid (55.0 g) and methanol (440 mL) were brought to reflux for 1 hour, cooled to room temperature and stirred for an additional 3 hours at ambient temperature. The slurry was filtered and the filter cake was washed with methanol (200 mL). The solid was air-dried and then dried invacuo at 30C. to a constant weight, yielding 49.6 g (90% recovery) of(S)-2-(3-ethoxy-4-methoxyphenyl)- 1 -(methylsulphonyl)-eth-2-ylamine-N-acety l-L-leucine salt (98.4% ee). ChiralHPLC (1/99 EtOH/20 mM KH2PO4 pH 7.0, Ultron Chiral ES-OVS from Agilent Technologies,150 mm 4.6 mm, 0.5 mL/min., 240 nm): 18.4 mm (S-isomer, 99.2%), 25.5 mm (R-isomer,0.8%) |
90% | General procedure: [0188] A 3 L 3 -necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with 2-(3-ethoxy-4-methoxyphenyl)-l - (methylsulphonyl)-eth-2-ylamine (137.0 g, 500 mmol), N-acetyl-L-leucine (52 g, 300 mmol), and methanol (1.0 L). The stirred slurry was heated to reflux for 1 hour. The stirred mixture was allowed to cool to ambient temperature and stirring was continued for another 3 hours at ambient temperature. The slurry was filtered and washed with methanol (250 L). The solid was air-dried and then dried in vacuo at ambient temperature to a constant weight, giving 109.5 g (98% yield) of the crude product (85.8% ee). The crude solid (55.0 g) and methanol (440 mL) were brought to reflux for 1 hour, cooled to room temperature and stirred for an additional 3 hours at ambient temperature. The slurry was filtered and the filter cake was washed with methanol (200 mL). The solid was air-dried and then dried in vacuo at 30 C to a constant weight, yielding 49.6 g | |
90% | In methanol; at 20℃; for 4h;Reflux; | A mixture of 2-(3-ethoxy-4-meth- oxyphenyl)-i -(methylsulphonyl)-eth-2-ylamine (137.0 g, 500 mmol), N-acetyl-L-leucine (52 g, 300 mmol), andmethanol (1.0 L) was charged into a 3-L 3-necked round bottom flask equipped with a mechanical stirrer, a thermometer, and a condenser. Afier the reaction mixture was refluxed for 1 hour, the mixture was allowed to cool to ambient temperature and then stirred for another 3 hours at ambient temperature. The slurry was filtered and washed with methanol (250 L). The solid was air-dried and then dried in vacuum at ambient temperature to a constant weight, giving 109.5 g (98% yield) of the crude product (85.8% cc). The crude solid (55.0 g) and methanol (440 mE) were brought to reflux for 1 hour, cooled to room temperature and stirred for an additional 3 hours at ambient temperature. The slurry was filtered and the filter cake was washed with methanol (200 mE). The solid was air-dried and then dried in vacuum at 30 C. to a constant weight, yielding 49.6 g (90% recovery) of (S)-2-(3-ethoxy- 4-methoxyphenyl)-i -(methylsulphonyl)-eth-2-ylamine-N- acetyl-L-leucine salt (98.4% cc). Chiral HPLC (1/99 EtOH/ 20 mM KH2PO4 pH 7.0, Ultron Chiral ES-OVS from Agilent Technologies, 150 mmx4.6 mm, 0.5 mE/mm., 240 nm): 18.4 mm (S-isomer, 99.2%), 25.5 mm (R-isomer, 0.8%). |
73.5% | at 60 - 70℃; for 2h; | In a 500 ml round bottom flask, 200 ml of methanol was added followed by 20 gms of 2-(3-ethoxy-4-methoxyphenyl)-l-(methanesulfonyl)-eth-2-ylamine. The reaction mass was stirred and 76 gms of N-Acetyl-L-Leucine added and reaction mass was stirred. The reaction mass was heated for 2 hours at 60 to 65C, After heating, the reaction masswas cooled at room temperature and it was stirred at room temperature for 3 to 4 hours. The slurry was filtered. Washed with 30 ml methanol, material was unloaded and dried under vacuum for 2 hours at 45C. Yield: 14.36 gm. Further, this material is purified with methanol. |
41% | In methanol; for 2h;Reflux; | A mixture of 27.3 g (100 mmol) of 1- (3-ethoxy-4-methoxy) phenyl-2-methanesulfonyl ethylamine (4), 10.4 g(60 mmol) of N-acetyl-L-leucine was dissolved in 200 mL of methanol, heated under reflux for 2 h, and then cooled to room temperature to a large amountThe slurry was precipitated, filtered and washed with methanol to give the crude product. The crude product was again dissolved in 80 mL of methanol, heated to reflux for 2 h, and cooled againTo a large amount of slurry to the slurry, filter, and wash the filter cake with methanol. The solid was dried in vacuo to give 9.1 g (41% recovery)(S) -1- (3-ethoxy-4-methoxy) phenyl-2-methanesulfonylethylamine N-acetyl-L-leucine salt (97.9% ee). |
35% | In methanol; for 1h;Inert atmosphere; Reflux; | Example 5: Preparation of (S)-1-(4-methoxy-3-ethoxyphenyl)-2-methanesulfonylethylamine N-acetyl-L-leucine salt (IV) A dry 1,000mL glass flask equipped with a mechanical stirrer, a thermometer, and a condenser was added 500g of methanol, 136 g (0.5mol) <strong>[253168-94-4](R,S)-1-(4-methoxy-3-ethoxyphenyl)-2-methanesulfonylethylamine</strong> (E.g. racemate III prepared in Example 1), and 86.5 g (0.5mol) N-acetyl-L-leucine under nitrogen protection. The solution was heated to reflux for 1 hour. The solution was then cooled to 10C and filtered. The resultant filtrate will be used as mother liquor in Example 6. The resulting filter cake was washed with 55g of cold methanol 10C and dried under vacuum to give 78.1 g of white solid (S)-1-(4-methoxy-3-ethoxyphenyl)-2-methanesulfonylethylamine N-acetyl-L-leucine salt (IV). Yield 35.0%, optical purity 99.8%. |
In methanol; at 20℃; for 8h;Heating / reflux; | A mixture of <strong>[253168-94-4]2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine</strong> (137.0 g, 500 mmol), N-acetyl-L-leucine (52 g, 300 mmol), and methanol (1.0 L) was charged into a 3-L 3-necked round bottom flask equipped with a mechanical stirrer, a thermometer, and a condenser. After the reaction mixture was refluxed for 1 hour, the mixture was allowed to cool to ambient temperature and then stirred for another 3 hours at ambient temperature. The slurry was filtered and washed with methanol (250 L). The solid was air-dried and then dried in vacuum at ambient temperature to a constant weight, giving 109.5 g (98% yield) of the crude product (85.8% ee). The crude solid (55.0 g) and methanol (440 mL) were brought to reflux for 1 hour, cooled to room temperature and stirred for an additional 3 hours at ambient temperature. The slurry was filtered and the filter cake was washed with methanol (200 mL). The solid was air-dried and then dried in vacuum at 30 C. to a constant weight, yielding 49.6 g (90% recovery) of (S)-<strong>[253168-94-4]2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine</strong>-N-acetyl-L-leucine salt (98.4% ee). Chiral HPLC (1/99 EtOH/20 mM KH2PO4 (at)pH 7.0, Ultron Chiral ES-OVS from Agilent Technologies, 150 mm×4.6 mm, 0.5 mL/min., (at)240 nm): 18.4 min (S-isomer, 99.2%), 25.5 min (R-isomer, 0.8%). | |
In methanol; | 6.2.3. Resolution of <strong>[253168-94-4]2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine</strong> A 3 L 3-necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with <strong>[253168-94-4]2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine</strong> (137.0 g, 500 mmol), N-acetyl-L-leucine (52 g, 300 mmol), and methanol (1.0 L). The stirred slurry was heated to reflux for 1 hour. The stirred mixture was allowed to cool to ambient temperature and stirring was continued for another 3 hours at ambient temperature. The slurry was filtered and washed with methanol (250 L). The solid was air-dried and then dried in vacuo at ambient temperature to a constant weight, giving 109.5 g (98% yield) of the crude product (85.8% ee). The crude solid (55.0 g) and methanol (440 mL) were brought to reflux for 1 hour, cooled to room temperature and stirred for an additional 3 hours at ambient temperature. The slurry was filtered and the filter cake was washed with methanol (200 mL). The solid was air-dried and then dried in vacuo at 30 C. to a constant weight, yielding 49.6 g (90% recovery) of (S)-<strong>[253168-94-4]2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine</strong>-N-acetyl-L-leucine salt (98.4% ee). Chiral HPLC (1/99 EtOH/20 mM KH2PO4pH 7.0, Ultron Chiral ES-OVS from Agilent Technologies, 150 mm*4.6 mm, 0.5 mL/min., 240 nm): 18.4 min (S-isomer, 99.2%), 25.5 min (R-isomer, 0.8%). | |
In methanol; at 20℃; for 4h;Reflux; | [0113j A 3 L 3-necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with 2-(3-ethoxy-4-methoxyphenyl)-1 - (methylsulphonyl)-eth-2-ylamine (137.0 g, 500 mmol), N-acetyl-L-leucine (52 g, 300 mmol), and methanol (1.0 L). The stirred slurry was heated to reflux for 1 hour. The stirred mixture was allowed to cool to ambient temperature and stirring was continued for another 3 hours at ambient temperature. The slurry was filtered and washed with methanol (250 L). The solid was air-dried and then dried in vacuo at ambient temperature to a constant weight, giving 109.5 g (98% yield) of the crude product (85.8% ee). The crude solid (55.0 g) and methanol (440 mL) were brought to reflux for 1 hour, cooled to room temperature and stirred for an additional 3 hours at ambient temperature. The slurry was filtered and the filter cake was washed with methanol (200 mL). The solid was air-dried and then dried in vacuo at 30 C to a constant weight, yielding 49.6 g (90% recovery) of (S)-2-(3 -ethoxy-4-methoxyphenyl)- 1 -(methylsulphonyl)-eth-2-ylamine -Nacetyl-L-leucine salt (98.4% ee). Chiral HPLC (1/99 EtOH/20 mM KH2PO4 pH 7.0, Ultron Chiral ES-OVS from Agilent Technologies, 150mm x 4.6 mm, 0.5 mL/min., 240 nm): 18.4 mm (S-isomer, 99.2%), 25.5 mm (R-isomer, 0.8%). | |
49.6 g | In methanol; for 1h;Reflux; | 6.2.3. Resolution of <strong>[253168-94-4]2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine</strong> A 3 L 3-necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with <strong>[253168-94-4]2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine</strong> (137.0 g, 500 mmol), N-acetyl-L-leucine (52 g, 300 mmol), and methanol (1.0 L). The stirred slurry was heated to reflux for 1 hour. The stirred mixture was allowed to cool to ambient temperature and stirring was continued for another 3 hours at ambient temperature. The slurry was filtered and washed with methanol (250 L). The solid was air-dried and then dried in vacuo at ambient temperature to a constant weight, giving 109.5 g (98% yield) of the crude product (85.8% ee). The crude solid (55.0 g) and methanol (440 mL) were brought to reflux for 1 hour, cooled to room temperature and stirred for an additional 3 hours at ambient temperature. The slurry was filtered and the filter cake was washed with methanol (200 mL). The solid was air-dried and then dried in vacuo at 30 C. to a constant weight, yielding 49.6 g (90% recovery) of (S)-<strong>[253168-94-4]2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine</strong>-N-acetyl-L-leucine salt (98.4% ee). |
In methanol; for 1h;Reflux; | Resolution of 2-(3-ethoxy-4-methoxyphenyl-1-(methylsulphonyl)-eth-2-ylamine A 3 L 3-necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with <strong>[253168-94-4]2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine</strong> (137.0 g, 500 mmol), N-acetyl-L-leucine (52 g, 300 mmol), and methanol (1.0 L). The stirred slurry was heated to reflux for 1 hour. The stirred mixture was allowed to cool to ambient temperature and stirring was continued for another 3 hours at ambient temperature. The slurry was filtered and washed with methanol (250 L). The solid was air-dried and then dried in vacuo at ambient temperature to a constant weight, giving 109.5 g (98% yield) of the crude product (85.8% ee). The crude solid (55.0 g) and methanol (440 mL) were brought to reflux for 1 hour, cooled to room temperature and stirred for an additional 3 hours at ambient temperature. The slurry was filtered and the filter cake was washed with methanol (200 mL). The solid was air-dried and then dried in vacuo at 30 C. to a constant weight, yielding 49.6 g (90% recovery) of (S)-<strong>[253168-94-4]2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine</strong>-N-acetyl-L-leucine salt (98.4% ee). | |
18 g | In methanol; at 25℃; for 4h;Reflux; | The compound of formula V 0. 1mol 200mL of methanol was added and the reaction flask was refluxed clear solution was added portionwise N- acetyl-L- leucine (0.06mol ), a large number of the resulting solid was refluxed 1h, cooled to 25 C, stirred 1h, filtered and the filter cake was dried in vacuo at 40 C 5h, to give a white solid 22. 6g; The solid was added to the reaction flask and 180mL of methanol, refluxed for 1h, cooled to 25 C, stirred for 1h, filtered and the filter cake in and dried in vacuo 40 C 5h, to give a white solid 18g, 40 C and dried in vacuo 5h, ee: 98 · 6% |
68 g | In methanol; at 25℃; for 2h;Reflux; | To a reaction mixture of 700 ml methanol and 100 grams (gm) (0.366 moles) of 1-(3-ethoxy-4- methoxy phenyl)-2-(methylsulfonyl) ethanamine, 38gm (0.2196 moles) of N-acetyl-L-leucine was charged. The reaction mixture was heated to reflux for 1 hour. The reaction mixture was cooled to 25C to 30C and stirred for 1 hour. The product was filtered and washed with 100 ml methanol.The obtained solid material was dried under vacuum at 30C to obtain (S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl) ethanamine N-acetyl-L-leucine salt.(Yield = 68.Ogms)R-isomer: 0.5% |
35 g | In methanol; at 60 - 65℃; for 1h; | To 1 liter RBF the product of example 3 or 4 (75 g; 0.2743 moles), N- acetyl-L-leucine (47.5 g ; 0.2743) and methanol (545 mL) were charged and the suspension was stirred at 60 C to 65 C for 1 hour, the suspension was cooled to room temperature and stirred for another 3 hours. The solid was filtered and dried under reduced pressure to obtain 60 g of title compound with chiral purity of 85% desired isomer. It was further purified by methanol to give 35 g of pure title compound having chiral purity 99.5%. |
In methanol; at 60 - 65℃; for 1h; | To 1 liter round bottom flask, 1-(3-ethoxy-4-methoxy-phenyl)-2-methylsulfonyl-ethanamine,N-acetyl-L-leucine and methanol were charged and the suspension was stirred at 60 C to 65C for 1 hour, the suspension was cooled to room temperature and stirred for another 3 hours.The solid was filtered and dried under reduced pressure to obtain the title compound withchiral purity of 85 % desired isomer. Yield: 40 %.It was further purified by methanol to give pure title compound having chiral purity 99.5% | |
49.6 g | In methanol; for 1h;Reflux; | A 3 L 3-necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with <strong>[253168-94-4]2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine</strong> (137.0 g, 500 mmol), N-acetyl-L-leucine (52 g, 300 mmol), and methanol (1.0 L). The stirred slurry was heated to reflux for 1 hour. The stirred mixture was allowed to cool to ambient temperature and stirring was continued for another 3 hours at ambient temperature. The slurry was filtered and washed with methanol (250 L). The solid was air-dried and then dried in vacuo at ambient temperature to a constant weight, giving 109.5 g (98% yield) of the crude product (85.8% ee). The crude solid (55.0 g) and methanol (440 mL) were brought to reflux for 1 hour, cooled to room temperature and stirred for an additional 3 hours at ambient temperature. The slurry was filtered and the filter cake was washed with methanol (200 mL). The solid was air-dried and then dried in vacuo at 30 C to a constant weight, yielding 49.6 g (90% recovery) of (S)-<strong>[253168-94-4]2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine</strong>-N-acetyl-L-leucine salt (98.4% ee). Chiral HPLC (1/99 EtOH/20 mM KH2PO4 pH 7.0, Ultron Chiral ES-OVS from Agilent Technologies, 150 mm x 4.6 mm, 0.5 mL/min., 240 nm): 18.4 min (S-isomer, 99.2%), 25.5 min (R-isomer, 0.8%). |
49.6 g | In methanol; for 1h;Reflux; | A 3 L 3-necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with <strong>[253168-94-4]2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine</strong> (137.0 g, 500 mmol), N-acetyl-L-leucine (52 g, 300 mmol), and methanol (1.0 L). The stirred slurry was heated to reflux for 1 hour. The stirred mixture was allowed to cool to ambient temperature and stirring was continued for another 3 hours at ambient temperature. The slurry was filtered and washed with methanol (250 L). The solid was air-dried and then dried in vacuo at ambient temperature to a constant weight, giving 109.5 g (98% yield) of the crude product (85.8% ee). The crude solid (55.0 g) and methanol (440 mL) were brought to reflux for 1 hour, cooled to room temperature and stirred for an additional 3 hours at ambient temperature. The slurry was filtered and the filter cake was washed with methanol (200 mL). The solid was air-dried and then dried in vacuo at 30 C to a constant weight, yielding 49.6 g (90% recovery) of (S)-<strong>[253168-94-4]2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine</strong>-N-acetyl-L-leucine salt (98.4% ee). Chiral HPLC (1/99 EtOH/20 mM KH2PO4 pH 7.0, Ultron Chiral ES-OVS from Agilent Technologies, 150 mm x 4.6 mm, 0.5 mL/min., 240 nm): 18.4 min (S-isomer, 99.2%), 25.5 min (R-isomer, 0.8%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sodium hydroxide; In dichloromethane; water; at 15 - 25℃; for 0.25h;pH 13 - 14; | Example 3 Preparation of (1S)-1-(3-Ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethylamine After a mixture of (1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethylamine N-acetyl-L-Leucine salt (1.10 kg, 2.46 moles), deionized water (4.40 L), and dichloromethane (DCM, 5.50 L) was charged into a reaction vessel, a solution of sodium hydroxide (196.0 g, 4.90 moles) in 1.00 L of deionized water was charged into the reaction vessel over about 5 minutes at 15-25 C. The resulting mixture was stirred for at least 10 minutes at 15-25 C. and then the aqueous and organic phases were allowed to separate. The pH of the upper aqueous phase was maintained or adjusted at pH 13-14. The phases were separated and the upper aqueous phase was extracted with DCM (2*4.4 L). The pH of the aqueous phase was maintained at 13-14 throughout the extractions. The DCM extracts were combined and washed with deionized water (3.3 L) until the pH of the aqueous phase reached 11 or less. DCM was removed under vacuum below 35 C. The water content of the residual solid should be <0.1% w/w as measured by Karl Fisher titration. The residual solid was dried azeotropically with more DCM. The solid was dried to a constant weight in vacuo at 30-35 C. to give (1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethylamine as a white powder (639.0-672.0 g, 95-100% yield). |
100% | With sodium hydroxide; In dichloromethane; water; at 15 - 25℃; for 0.25h; | [011 8j After a mixture of (1 S)- 1 -(3 -ethoxy-4-methoxyphenyl)-2-methanesulfonyl- ethylamine N-acetyl-L-Leucine salt (1.10 kg, 2.46 moles), deionized water (4.40 L), and dichloromethane (DCM, 5.50 L) was charged into a reaction vessel, a solution of sodium hydroxide (196.0 g, 4.90 moles) in 1.00 L of deionized water was charged into the reaction vessel over about 5 minutes at 15-25C. The resulting mixture was stirred for at least 10 minutes at 15-25C and then the aqueous and organic phases were allowed to separate. The pH of the upper aqueous phase was maintained or adjusted at pH 13-14. The phases were separated and the upper aqueous phase was extracted with DCM (2x4.4 L). The pH of the aqueous phase was maintained at 13-14 throughout the extractions. The DCM extracts were combined and washed with deionized water (3.3 L) until the pH of the aqueous phase reached 11 or less. DCM was removed under vacuum below 35C. The water content of the residual solid should be <0.1% w/w as measured by Karl Fisher titration. The residual solid was dried azeotropically with more DCM. The solid was dried to a constant weight in vacuo at 30-35C to give (1S)-1-(3-ethoxy-4- methoxyphenyl)-2-methanesulfonyl-ethylamine as a white powder (639.0-672.0 g, 95-100% yield). |
100% | With sodium hydroxide; In dichloromethane; water; at 15 - 25℃; for 0.25h; | 6.5.3. Preparation of (1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethylamine After a mixture of (1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethylamine N-acetyl-L-Leucine salt (1.10 kg, 2.46 moles), deionizer water (4.40 L), and dichloromethane (DCM, 5.50 L) was charged into a reaction vessel, a solution of sodium hydroxide (196.0 g, 4.90 moles) in 1.00 L of deionizer water was charged into the reaction vessel over about 5 minutes at 15-25 C. The resulting mixture was stirred for at least 10 minutes at 15-25 C. and then the aqueous and organic phases were allowed to separate. The pH of the upper aqueous phase was maintained or adjusted at pH 13-14. The phases were separated and the upper aqueous phase was extracted with DCM (2*4.4 L). The pH of the aqueous phase was maintained at 13-14 throughout the extractions. The DCM extracts were combined and washed with deionizer water (3.3 L) until the pH of the aqueous phase reached 11 or less. DCM was removed under vacuum below 35 C. The water content of the residual solid should be <0.1% w/was measured by Karl Fisher titration. The residual solid was dried azeotropically with more DCM. The solid was dried to a constant weight in vacuo at 30-35 C. to give (1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethylamine as a white powder (639.0-672.0 g, 95-100% yield). |
99.3% | With sodium hydroxide; In dichloromethane; at 0 - 5℃; for 2h; | Example 7: Preaparation of (S)-1-(4-methoxy-3-ethoxyphenyl)-2-methanesulfonylethylamine (II) Into a 200 ml glass flask was added sequentially 500g of dichloromethane, 44.5g (0.1mol) (S)-1-(4-methoxy-3-ethoxyphenyl)-2-methanesulfonylethylamine N-acetyl-L-leucine salt (IV) (prepared as described in Example 5), and 11g of 40% sodium hydroxide. The reaction was stirred at 0-5C for 2 hours. The solution was extracted with dichloromethane. 3g of dichloromethane phase was dried over anhydrous sodium sulfate and filtered. After distilling off the dichloromethane, 27.1g (S)-1-(4-methoxy-3-ethoxyphenyl)-2-methanesulfonylethylamine (II) was obtained. Optical purity 99.9%, Yield 99.3%. |
95-100% | With sodium hydroxide; In dichloromethane; water; | 6.5.3. Preparation of (1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethylamine After a mixture of (1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethylamine N-acetyl-L-Leucine salt (1.10 kg, 2.46 moles), deionized water (4.40 L), and dichloromethane (DCM, 5.50 L) was charged into a reaction vessel, a solution of sodium hydroxide (196.0 g, 4.90 moles) in 1.00 L of deionized water was charged into the reaction vessel over about 5 minutes at 15-25 C. The resulting mixture was stirred for at least 10 minutes at 15-25 C. and then the aqueous and organic phases were allowed to separate. The pH of the upper aqueous phase was maintained or adjusted at pH 13-14. The phases were separated and the upper aqueous phase was extracted with DCM (2*4.4 L). The pH of the aqueous phase was maintained at 13-14 throughout the extractions. The DCM extracts were combined and washed with deionized water (3.3 L) until the pH of the aqueous phase reached 11 or less. DCM was removed under vacuum below 35 C. The water content of the residual solid should be <0.1% w/was measured by Karl Fisher titration. The residual solid was dried azeotropically with more DCM. The solid was dried to a constant weight in vacuo at 30-35 C. to give (1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethylamine as a white powder (639.0-672.0 g, 95-100% yield). |
94% | With sodium carbonate; In water;pH 10; | To a solution of 102-A ((S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl) ethanamine (S)-2-acetamido-4-methylpentanoate, 800 mg, 1.79 mmol) in H2O (10 mL) was added saturated aqueous solution of Na2CO3 to pH = 10,then the mixture was extracted with EtOAc (30 mL2). The combined EtOAc solution was dried, filtered and concentratedto give compound 102-B ((S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl) ethanamine, 460 mg, yield: 94%) asyellow solid.1H NMR (300 MHz, DMSO-d6) delta 7.02 (s, 1H), 6.89 (s, 2H), 4.27 (dd, J = 9.3, 3.6 Hz, 1H), 3.99-4.06 (m, 2H), 3.73 (s,3H), 3.20-3.45 (m, 2H), 2.95 (s, 3H), 2.16 (s, 2H), 1.27-1.35 (m, 3H). |
With sodium hydroxide; In dichloromethane; water; at 15 - 25℃; for 0.25h; | [0193] After a mixture of (1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl- ethylamine N-acetyl-L-Leucine salt (1.10 kg, 2.46 moles), deionized water (4.40 L), and dichloromethane (DCM, 5.50 L) was charged into a reaction vessel, a solution of sodium hydroxide (196.0 g, 4.90 moles) in 1.00 L of deionized water was charged into the reaction vessel over about 5 minutes at 15-25C. The resulting mixture was stirred for at least 10 minutes at 15-25C and then the aqueous and organic phases were allowed to separate. The pH of the upper aqueous phase was maintained or adjusted at pH 13-14. The phases were separated and the upper aqueous phase was extracted with DCM (2x4.4 L). The pH of the aqueous phase was maintained at 13-14 throughout the extractions. The DCM extracts were combined and washed with deionized water (3.3 L) until the pH of the aqueous phase reached 11 or less. DCM was removed under vacuum below 35C. The water content of the residual solid should be <0.1% w/w as measured by Karl Fisher titration. The residual solid was dried azeotropically with more DCM. The solid was dried to a constant weight in vacuo at 30-35C to give (lS)-l-(3-ethoxy-4- methoxyphenyl)-2-methanesulfonyl-ethylamine as a white powder (639.0-672.0 g, 95-100% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.3% | In methanol; for 1h;Reflux; | Under a nitrogen atmosphere, a dry 1000 ml glass flask equipped with a mechanical stirrer, a thermometer and a condenser was added (S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethylamine (110 g), N-acetylleucine 69.3 g (0.4 mol) and 500g of methanol, Heated to reflux for 1 hour with stirring and then cooled to ambient temperature in a stirred state and stirred at room temperature for 3 hours, filtered and the filter cake was washed with methanol, then the cake was dried under vacuum to constant weight. To give 176.3 g of (S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethylamine N-acetyl-1-leucine (Optical purity 99.6%) yield 98.3%. Chiral HPLC (ethanol: 20 mM KH2PO4 = 1:99, pH = 7.0, Agilent's ES-OVM chiral column, 150 mm x 4.6 mm, flow rate 0.5 ml/min, detection wavelength 240 nm): 18.1 min (S-isomer, 99.6%), 25.0 min (R-isomer, 0.4%). |
In methanol; at 65 - 70℃; | Compound <strong>[608141-42-0](S)-2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulfonyl)-eth-2-ylamine</strong> N-acetyl-L-leucine salt specific preparation methods are: Reaction temperature 65 ~ 70 deg.C. Under 420ml methanol selected as a solvent condition, 60g of the compound 2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulfonyl)-eth-2-ylamine and 22g compound N-acetyl-L-leucine salt formation reaction to give the compound 60g <strong>[608141-42-0](S)-2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulfonyl)-eth-2-ylamine</strong> N-acetyl-L-leucine salt. Compound (S) -2- (3- ethoxy-4-methoxyphenyl) -1- (methylsulfonyl) - ethyl 2-acetyl-amine -N- -L- leucine salt specific purification methods are: reaction temperature 65 ~ 70 , 420ml methanol as the choice of solvent, at the reflux temperature of the purified purified (S) -2- (3- ethoxy-4-methoxyphenyl) -1 - (methylsulfonyl) - ethyl 2-acetyl-amine -N- -L- leucine salts, reflux temperature was 70 deg.C . | |
1670 g | In methanol; for 1h;Reflux; | To a stirred solution l-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanamine (2500gm) in methanol (20.01it) was added N-acetyl-L-Leucine (950.0gm) slowly at 25C and then the reaction mixture was heated to reflux temperature and maintained for 1.Ohr. The reaction mass was cooled to 25-30C and stirred for 4.0 hr at 25-30C. The product was filtered and washed with methanol and dried under vacuum at 60C for 4.0 hr to obtain 2000.0gm of crude product. The crude product was subjected to methanol purification to obtain 1670gm of N-acetyl L-leucine salt of (5)-2-(3-ethoxy-4- methoxyphenyl)-l-(methylsulphonyl) eth-2-ylamine. chiral purity >99.5%. |
[ 608141-42-0 ]
(S)-1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanamine