4-bromo-2-chlorobenzoyl chloride

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 6,11-dihydro-5H-pyrido[2,3-b][1,5] benzodiazepine (3 g, 15.2 mmol) in N,N-dimethylformamide under nitrogen were added solid potassium carbonate (6.3 g, 45.6 mmol). The mixture was treated dropwise with a solution of the crude 4-bromo-2-chlorobenzoyl chloride (22.9 mmol) in N,N-dimethylformamide. After stirring at room temperature for 15 minutes, water was added under stirring. The resulting solid was collected, dissolved in chloroform, and the solution washed with 1N NaOH and brine. The organic layer was dried over anhydrous sodium sulfate and evaporated to dryness. The residue (purple foam) was dissolved in dichloromethane and absorbed onto a silica Merck-60 flash column. Elution with 20% ethyl acetate in hexane provided 3.4 g of the title compound as a foam which crystallized as a white solid by trituration from ethanol-ether, m.p. 165-168° C. under stirring The resulting solid was collected dissolved in chloroform the solution washed with 1N NaOH and brine The organic layer was dried over anhydrous sodium sulfate evaporated to dryness The residue (purple foam) was dissolved in dichloromethane absorbed onto a silica Merck-60 flash column Elution with 20% ethyl acetate in hexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 10,11-dihydro-5H-pyrrolo [2,1-c][1,4] benzodiazepine (1.44 g) and triethylamine (0.95 g) in dichloromethane (40 mL) cooled in an ice bath, was added dropwise a solution of the crude 4-bromo-2-chlorobenzoyl chloride (2.42 g) in dichloromethane (20 mL). The cooling bath was removed and after stirring for 22 hours, the reaction mixture was sequentially washed with water, saturated aqueous sodium bicarbonate, 0.5 N hydrochloric acid and water. The dichloromethane solution was dried over anhydrous sodium sulfate, filtered and then evaporated to dryness to yield an off-white foam. Purification by flash chromatography on silica gel Merck-60 eluting with hexane-ethyl acetate (2:1) resulted in a white solid (3.02 g), m.p. 77-80° C. cooled in an ice bath The cooling bath was removed the reaction mixture was sequentially washed with water, saturated aqueous sodium bicarbonate, 0.5 N hydrochloric acid and water The dichloromethane solution was dried over anhydrous sodium sulfate filtered evaporated to dryness to yield an off-white foam Purification by flash chromatography on silica gel eluting with hexane-ethyl acetate (2:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 7.2 g of aluminium chloride are added to 80 ml of nitrobenzene at 5° C. and a solution of 8 g of 4-bromo-2-chloro-benzoyl chloride in 20 ml of nitrobenzene is added dropwise in such a manner that the temperature does not exceed 10° C. After stirring and adding 3.26 ml of anisole the reaction mixture is warmed to room temperature, stirred and subsequently poured on to ice-water and extracted with methylene chloride. The extracts are washed with saturated sodium chloride solution, dried and evaporated. There are obtained 10.0 g of (4-bromo-2-chloro-phenyl)-(4-methoxy-phenyl)-methanone, MS: m/e 324 (M+H+, 1 Br). does not exceed 10° C stirred extracted with methylene chloride The extracts are washed with saturated sodium chloride solution dried evaporated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The starting material was prepared by conventional procedures starting from the lithium salt of monoethyl malonate and 4-bromo-2-chlorobenzoyl chloride which reacted to form ethyl 4-bromo-2-chlorobenzoylacetate. The latter was caused to react with dimethylformamide dimethylacetal to give ethyl 3-dimethylamino-2-(4-bromo2-chlorobenzoyl)propenoate, which by reaction with 4-fluoroaniline afforded said starting material. The starting material was prepared by conventional procedures reacted

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The starting material was prepared by conventional procedures starting from the lithium salt of monoethyl malonate and 4-bromo-2-chlorobenzoyl chloride which reacted to form ethyl 4-bromo-2-chlorobenzoylacetate. The latter was caused to react with dimethylformamide dimethylacetal to give ethyl 3-dimethylamino-2-(4-bromo2-chlorobenzoyl)propenoate, which by reaction with 4-fluoroaniline afforded said starting material. The starting material was prepared by conventional procedures reacted

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 13bs) 6.8 g of monoethyl malonate potassium salt in 70 ml of acetonitrile were cooled to 10° under argon and treated with 5.3 ml of triethylamine and 4.8 g of magnesium chloride. The resulting thick suspension was stirred at room temperature for 2 hrs. Then, it was again cooled to 10° and 5 g of 4-bromo-2-chloro-benzoyl chloride were added dropwise thereto over 30 min. The mixture was stirred at room temperature for 15 hrs. and then concentrated. Extraction: twice with 100 ml of toluene, once with 100 ml of cold 1N HCl and twice with 100 ml of water. After drying and evaporation there were obtained 5.2 g (85%) of ethyl 3-(4-bromo-2-chlorophenyl)-3-oxo-propionate as a brown oil which crystallized in a refrigerator. M.p. 34° C. Then, it was again cooled to 10° over 30 min The mixture was stirred at room temperature for 15 hrs and then concentrated Extraction After drying evaporation there

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 13bs) 6.8 g of monoethyl malonate potassium salt in 70 ml of acetonitrile were cooled to 10° under argon and treated with 5.3 ml of triethylamine and 4.8 g of magnesium chloride. The resulting thick suspension was stirred at room temperature for 2 hrs. Then, it was again cooled to 10° and 5 g of 4-bromo-2-chloro-benzoyl chloride were added dropwise thereto over 30 min. The mixture was stirred at room temperature for 15 hrs. and then concentrated. Extraction: twice with 100 ml of toluene, once with 100 ml of cold 1N HCl and twice with 100 ml of water. After drying and evaporation there were obtained 5.2 g (85%) of ethyl 3-(4-bromo-2-chlorophenyl)-3-oxo-propionate as a brown oil which crystallized in a refrigerator. M.p. 34° C. Then, it was again cooled to 10° over 30 min The mixture was stirred at room temperature for 15 hrs and then concentrated Extraction After drying evaporation there