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CAS No. : | 42860-10-6 | MDL No. : | MFCD00079706 |
Formula : | C7H4BrClO2 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | NLEPZGNUPNMRGF-UHFFFAOYSA-N |
M.W : | 235.46 | Pubchem ID : | 2735544 |
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 |
---|---|---|
With thionyl chloride;N,N-dimethyl-formamide; at 80℃; for 2h; | Example 4; (Method C) <n="51"/>Example 4aSynthesis of 3-Bromo-4-chlorobenzamideTo a mixture of S-bromo^-chlorobenzoic acid (5.07 g, 22 mmol, Alfa Aesar) and thionyl chloride (15 ml, 206 mmol) was added 1 drop of DMF and the reaction was heated at 80 0C. After 2 h the excess SOCl2 was removed in vacuo and the residue was azeotroped with toluene (2x). The residue was dissolved in 40 mL OfCH2Cl2 and cooled to 0 0C. Ammonia was bubbled into the reaction for 30 min. The mixture was diluted with 200 mL Of CH2Cl2 and washed with saturated NaHCO3. The aqueous layer was extracted with CH2Cl2 (3x) and the combined organic layers were washed with H2O and dried over Na2SO4 to give 3.81 g (75percent) of a white amorphous solid. MS- m/z: 233.9, 235.9 [M+l]. | |
With oxalyl dichloride; In dichloromethane; N,N-dimethyl-formamide; at 20 - 40℃; for 1h; | Step 1. To a solution of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> 71 (5.30 g, 23 mmol) in DCM (10 mL) at room temperature was added DMF (5 drops) and oxalyl dichloride (3.0 mL, 34 mmol). The reaction mixture was heated to 40° C. for 1 h. The solvent and excess oxalyl chloride were removed under a stream of nitrogen followed by high vacuum. The acid chloride was dissolved in DCM (100 mL), cooled to 0° C., and then pyridine (2.8 mL, 34 mmol) was added followed by (R)-1-phenylethanamine (3.8 mL, 30 mmol). The reaction mixture was stirred at 0° C. for 1 h and concentrated under reduced pressure. The crude amide was dissolved in EtOAc, washed with 1 M HCl (2*), brine (1*), dried over MgSO4, filtered, and concentrated to give (R)-3-bromo-4-chloro-N-(1-phenylethyl)benzamide 72 (8.15 g, 71percent yield) as a white solid which was used without further purification. Mass spectrum: calculated for C15H13BrClNO 337.0; found 338.0 (M++1). | |
With thionyl chloride; In dichloromethane; N,N-dimethyl-formamide; at 0 - 20℃; for 2h; | Step 1. A solution of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> 104 (2.354 g, 10.0 mmol) in 30 mL of CH2Cl2 was chilled to 0° C. in an ice bath. To this solution was added a solution of thionyl chloride (2.2 mL, 30 mmol) in CH2Cl2 and then a few drops of DMF. The reaction was warmed to room temperature and stirred under N2 for 2 h. The reaction mixture was concentrated in vacuo. The crude acid chloride was re-dissolved in CH2Cl2 and it was chilled to 0° C. Triethylamine (2.8 mL, 20 mmol) was slowly added to the reaction via syringe. The reaction was warmed to room temperature and stirred for 2 h under N2. The reaction mixture was concentrated and then diluted with EtOAc. The solution was extracted with saturated NaHCO3, water, and brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified by ISCO flash chromatography using a 5percent to 60percent gradient of EtOAc in hexanes as the eluant. The desired fractions were combined and concentrated to give 3-bromo-4-chloro-N-methoxy-N-methylbenzamide 105 (2.43 g, 87percent yield) as a colorless oil. |
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃; | Example 77 3-Bromo-4-chlorobenzamide 3-Bromo-4-chlorobenzoic acid (2.35 g, 10 mmol) was suspended in CH2Cl2 (50 mL) and stirred under argon at room temperature. Oxalyl chloride (2.53 g, 20 mmol) was added followed by DMF (10 muL). Gas evolution began, and the mixture was stirred until gas evolution ceased. The solvents were pumped off and toluene was added and stripped off to remove excess oxalyl chloride. The residue was taken up in EtOAc and added to concentrated ammonium hydroxide (10 mL). This was stirred for 30 min. The phases were separated and the organic washed 1* with brine dried over anhydrous Na2SO4, filtered, and evaporated. The residue was crystallized from EtOAc/hexane to give the title compound as a white crystalline solid. LC-MS m/z 233.7 (M+H)+, 1.54 min (ret time); mp 146-147° C.; analytical HPLC shows 100percent purity, (ret time: 11.835 min). | |
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃;Inert atmosphere; | Example 94 3-Bromo-4-chlorobenzamide 3-Bromo-4-chlorobenzoic acid (2.35 g, 10 mmol) was suspended in CH2Cl2 (50 mL) and stirred under argon at room temperature. Oxalyl chloride (2.53 g, 20 mmol) was added followed by DMF (10 muL). Gas evolution began, and the mixture was stirred until gas evolution ceased. The solvents were pumped off and toluene was added and stripped off to remove excess oxalyl chloride. The residue was taken up in EtOAc and added to concentrated ammonium hydroxide (10 mL). This was stirred for thirty min. The phases were separated and the organic washed 1* with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The residue was crystallized from EtOAc/hexane to give the title compound as a white crystalline solid. LC-MS m/z 233.7 (M+H)+, 1.54 min (ret time); mp 146-147° C.; analytical HPLC shows 100percent purity, (ret time 11.835 min). | |
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃;Inert atmosphere; | Example 77 3-Bromo-4-chlorobenzamide3-Bromo-4-chlorobenzoic acid (2.35 g, 10 mmol) was suspended in CH2Cl2 (SO mL) and stirred under argon at room temperature. Oxalyl chloride (2.53 g, 20 mmol) was added followed by DMF (10 muL). Gas evolution began, and the mixture was stirred until gas evolution ceased. The solvents were pumped off and toluene was added and stripped off to remove excess oxalyl chloride. The residue was taken up in EtOAc and added to concentrated ammonium hydroxide (10 mL). This was stirred for 30 min. The phases were separated and the organic washed IX with brine dried over anhydrous Na2SO4, filtered, and evaporated. The residue was crystallized from EtOAc/hexane to give the title compound as a white crystalline solid. LC-MS m/z 233.7 (M+H)+, 1.54 min (ret time); mp 146-147 0C; analytical HPLC shows 100percent purity, (ret time: 11.835 min). | |
With thionyl chloride; sodium chloride; In ethyl acetate; for 5h;Reflux; Inert atmosphere; | To a stirred suspension of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> (0.5 g) in EtOAc (10 mL) NaCl was added followed by the addition of 0.77 mL of thionyl chloride. This heterogeneous reaction mixture was then refluxed. After 5 hours, the reaction was cooled to room temperature and the volatiles were removed under reduced pressure. Excess solvent was removed and the residue was taken up in THF (10 mL) and cooled in an ice bath. Solid sodium cyanamide (0.272 g) was added to this stirred solution portionwise and the reaction was allowed to stir for twelve hours. Then THF was removed under reduced pressure and 15 mL of water was added to the residue. The solid was filtered off and the filtrate was acidified with IN aq. HC1. The precipitated white solid was isolated, filtered, and dried. Compound S3 was carried forward without additional purification. | |
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; for 1h; | To <strong>[42860-10-6]3-bromo-4-chloro-benzoic acid</strong> (9.4 g, 40 mmol ) in dry DCM (100 mL), was added DMF (0.5 ml.) followed by addition of oxalyl chloride (22.5 ml_, 55 mmol, 2M in DCM ) slowly. The mixture was stirred for 1 hr, then concentrated to yield 3-bromo-4-chloro-benzoyl chloride as an off-white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In 1,4-dioxane; for 24h;Heating / reflux; | Example 9A. 3-Bromo-4-chlorobenzoic acid ethyl ester.To a solution of <strong>[42860-10-6]3-bromo-4-chlorobenzoic acid</strong> (5.0 g, 21 mmol) in 150 mL absolute ethanol was added 15 mL of 4N HCl/dioxane. The mixture was heated to reflux for 24 hours then cooled to ambient temperature and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and H2O, and the separated organic phase was washed sequentially with saturated NaHCpsi3 solution, brine, dried (Na2SO-O, filtered and concentrated under reduced pressure to provide the title compound. 1H NMR (DMSO-ddelta) delta 8.22 (d, IH), 7.94 (dd, IH), 7.80 (d, IH), 4.33 (q, 2H), 1.33 (t, 3H); MS (DCI4) m/z 263 (M+H)+. |
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