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CAS No. : | 75416-51-2 | MDL No. : | MFCD10001500 |
Formula : | C9H10BrN | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | KHWGHUZYXQPIKA-UHFFFAOYSA-N |
M.W : | 212.09 | Pubchem ID : | 12630420 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | Packing Group: | |
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 |
---|---|---|
To a mixture of 6-bromo-1,2,3,4-tetrahydroisoquinoline and 8-bromo-1,2,3,4-tetrahydroisoquinoline (22.1 mmol) in THF (100 mL) was added DIPEA (22.1 mmol) and BOC2O (24 mmol). The reaction mixture was allowed to stir at rt over the weekend and then concentrated. Water (5 mL) was added to the residue and the pH was adjusted to 2 by the addition of 1N H3PO4. The mixture was extracted with EtOAc. The organic solutions were combined, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give tert-butyl 6-bromo-3,4-dihydroisoquinoline-2(1H)-carboxylate and tert-butyl 8-bromo-3,4-dihydroisoquinoline-2(1H)-carboxylate (6.04 g, 88%) as a yellow oil. | ||
Dry THF (50 mL) and DIPEA (1.3 mL, 7.5 mmol) were added followed by BOC- anhydride (1.8 g, 8.2 mmol). The mixture was stirred overnight at RT. The volatiles were evaporated and the residue was taken up in water. The pH was adjusted to 2 with IM phosphoric acid and the product was extracted twice with EtOAc. The combined organic phases were washed with brine made slightly alkaline with saturated sodium bicarbonate, dried, filtered and concentrated. The crude product was purified by column chromatography with EtOAc-heptanes (1:50 through 1:20) to give 2.24 g (96%) of a 3:1 mixture of the title product and fert-butyl 8-bromo-3,4-dihydroisoquinoline-2(lH)- carboxylate. EPO <DP n="26"/>LC-MS m/z 256/258 (M-56);1H NMR (CDCl3) delta 7.31 (dd, IH), 7.30 (br s, IH), 6.98 (d, IH), 4.52 (s, 2H), 3.63 (t, 2H), 2.81 (t, 2H) and 1.50 (s, 9H) ppm (6-isomer).1H NMR (CDCl3) delta 7.42 (dd, IH), 7.12-7.01 (m's, 2H), 4.55 (s, 2H), 3.64 (t, 2H), 2.84 (t, 2H) and 1.51 (s, 9H) ppm (8-isomerV | ||
Dry THF (50 mL) and DIPEA (1.3 mL, 7.5 mmol) were added followed by BOC- anhydride (1.8 g, 8.2 mmol). The mixture was stirred at RT overnight. The volatiles were i5 evaporated and the residue was taken up in water. The pH was adjusted to 2 with IM phosphoric acid and the product was extracted twice with EtOAc. The combined organic phases were washed with brine made slightly alkaline with saturated sodium bicarbonate, dried, filtered and concentrated. The crude product was purified by column chromatography with EtOAc-heptanes (1:50 through 1:20) to give 2.24 g (96%) of a 3:120 mixture of the title product and tert-butyl 8-bromo-3,4-dihydroisoquinoline-2(lH)- carboxylate. LC-MS mlz 256, 258 (M-56);1H NMR (CDCl3) delta 7.31 (dd, IH), 7.30 (br s, IH), 6.98 (d, IH), 4.52 (s, 2H), 3.63 (t, 2H),2.81 (t, 2H) and 1.50 (s, 9H) ppm (6-isomer).25 11HH N NMMRR ( (CCDDCCll33)) delta delta 77..4422 ( (dddd,, I IHH)),, 77..112-7.01 (m, 2H), 4.55 (s, 2H), 3.64 (t, 2H), 2.84 (t, 2H) and 1.51 (s, 9H) ppm (8-isomer). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With triethylamine; In dichloromethane; at 0 - 20℃; for 0.5h; | Boc2O (25.73 g, 117.88 mmol) was added dropwise to a solution of intermediate 21 (25.00 g, 117.88 mmol) and TEA (32.83 mL, 236.00 mmol) in DCM (300 mL) at 0 °C. The resulting mixture was stirred at room temperature for 30 minutes. Sat. citric acid was added to quench the reaction and layers were separated. The organic layer was washed with brine, dried over Mg504, filtered and evaporated in vacuo. The crude residue was purified by silica gel column (mobile phase: Petroleum ether/EtOAc, 3/1, v/v) to give 35 g of intermediate 22 (95percent yield). |
80% | With sodium hydrogencarbonate; In tetrahydrofuran; at 20℃; | 8-Bromo-1,2,3,4-tetrahydroisoquinoline 14.1 (200 mg, 0.804 mmol) was suspended in tetrahydrofuran (4 ml) and saturated sodium bicarbonate (2 ml) then di-t-butyl dicarbonate (263 mg, 1.21 mmol) was added as a solution in THF (2 ml) and the mixture was stirred atRT for 42 h. The reaction mixture was poured into water and extracted three times with ethyl acetate. The organic extract was dried over sodium sulfate, filtered and evaporated. The residue was purified via flash silica chromatography (heptane I DCM 0-80percent) to provide compound 14.2 (200 mg, 80percent) as a colourless oil. 1H NMR (ODd3, 400 MHz) O 1.30 (5, 9H), 2.82 (m, 2H), 3.63 (m, 2H), 4.60 (m, 2H), 7.05 (m, 2H), 7.39 (d, 1H). UPLC-MS (shortbasic) rt 1.01 (255, 257 [M-tBu+H]), 96percent pure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | NaBH3CN (30.20 g, 480.64 mmol) was added to a mixture of <strong>[63927-22-0]8-bromoisoquinoline</strong>(20.00 g, 96.13 mmol) in MeOH (300 mL) at 0 °C. The resulting mixture was stirredfor 10 minutes and Boron trifluoride diethyl etherate (68.22 g, 480.64 mmol) was added dropwise at 0 °C. The resulting mixture was stirred for 1 hour at 0 °C and then refluxed for 4 hours. Sat. Na2CO3 (5 mL) was added and solvent was concentrated under reduced pressure. The remaining liquid was poured into water and extracted withCH2C12. The organic layer was washed with brine, dried over Mg504, filtered and evaporated in vacuo to give 20 g of intermediate 21(98percent yield) which was used in the next step without further purification. |
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