2-(5-bromo-2-methylphenyl)acetyl chloride

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

実験手順: 3.00 g (11.75 mmol) of methyl 1-amino-4-methoxy-4-(trifluoromethyl)cyclohexanecarboxylate (Example 22A) and 1.19 g (11.75 mmol) of triethylamine were dissolved in 40 ml of dichloromethane. 2.65 g (10.69 mmol) of (5-bromo-2-methylphenyl)acetyl chloride (Example 3A), dissolved in 40 ml of dichloromethane, were added dropwise to this solution, and the reaction mixture was stirred at room temperature overnight. For work-up, the mixture was diluted with dichloromethane and the organic phase was washed with aqueous saturated sodium bicarbonate solution and with aqueous 1% strength citric acid. After drying over sodium sulphate, the organic phase was concentrated and the product was dried. This gave 4.79 g (87% of theory) of the title compound as a beige powder. were added dropwise to this solution the organic phase was washed with aqueous saturated sodium bicarbonate solution and with aqueous 1% strength citric acid After drying over sodium sulphate the organic phase was concentrated the product was dried

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

実験手順: At room temperature, 5.47 g (25.41 mmol) of methyl 8-amino-1,4-dioxaspiro[4.5]decane-8-carboxylate [T. Satoh et al., Tetrahedron 63 (2007), 4806-4813], 3.86 g (38.12 mmol) of triethylamine and 155 mg (1.27 mmol) of N,N-dimethylaminopyridine were dissolved in 45 ml of dichloromethane. A solution of 6.29 g (25.41 mmol) of (5-bromo-2-methylphenyl)acetyl chloride (Example 3A) in 45 ml of dichloromethane was then added dropwise to the mixture. The resulting reaction mixture was stirred at room temperature overnight. For work-up, the mixture was diluted with dichloromethane and the organic phase was washed with aqueous saturated sodium bicarbonate solution. After drying over sodium sulphate, the mixture was concentrated by evaporation and the residue was purified by chromatography on silica gel (mobile phase: hexane/ethyl acetate gradient/1% triethylamine) Evaporation and drying gave 3.64 g (34% of theory) of the title compound which was used without further characterization in the next step. The resulting reaction mixture the organic phase was washed with aqueous saturated sodium bicarbonate solution After drying over sodium sulphate the mixture was concentrated by evaporation the residue was purified by chromatography on silica gel (mobile phase: hexane/ethyl acetate gradient/1% triethylamine) Evaporation drying

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6.00 g (26.19 mmol) of (5-bromo-2-methylphenyl)acetic acid (EP 1791816 A1 and US 2006/29799 A1) were dissolved in 31.20 g (261.92 mmol) of thionyl chloride. The reaction mixture was stirred at 80° C. for two hours and then concentrated under reduced pressure. Drying under fine vacuum gave 6.29 g (97% of theory) of the title compound as a brownish oil. concentrated under reduced pressure Drying under fine vacuum

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

実験手順: 3.00 g (11.75 mmol) of methyl 1-amino-4-methoxy-4-(trifluoromethyl)cyclohexanecarboxylate (Example 22A) and 1.19 g (11.75 mmol) of triethylamine were dissolved in 40 ml of dichloromethane. 2.65 g (10.69 mmol) of (5-bromo-2-methylphenyl)acetyl chloride (Example 3A), dissolved in 40 ml of dichloromethane, were added dropwise to this solution, and the reaction mixture was stirred at room temperature overnight. For work-up, the mixture was diluted with dichloromethane and the organic phase was washed with aqueous saturated sodium bicarbonate solution and with aqueous 1% strength citric acid. After drying over sodium sulphate, the organic phase was concentrated and the product was dried. This gave 4.79 g (87% of theory) of the title compound as a beige powder. were added dropwise to this solution the organic phase was washed with aqueous saturated sodium bicarbonate solution and with aqueous 1% strength citric acid After drying over sodium sulphate the organic phase was concentrated the product was dried

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

実験手順: At room temperature, 5.47 g (25.41 mmol) of methyl 8-amino-1,4-dioxaspiro[4.5]decane-8-carboxylate [T. Satoh et al., Tetrahedron 63 (2007), 4806-4813], 3.86 g (38.12 mmol) of triethylamine and 155 mg (1.27 mmol) of N,N-dimethylaminopyridine were dissolved in 45 ml of dichloromethane. A solution of 6.29 g (25.41 mmol) of (5-bromo-2-methylphenyl)acetyl chloride (Example 3A) in 45 ml of dichloromethane was then added dropwise to the mixture. The resulting reaction mixture was stirred at room temperature overnight. For work-up, the mixture was diluted with dichloromethane and the organic phase was washed with aqueous saturated sodium bicarbonate solution. After drying over sodium sulphate, the mixture was concentrated by evaporation and the residue was purified by chromatography on silica gel (mobile phase: hexane/ethyl acetate gradient/1% triethylamine) Evaporation and drying gave 3.64 g (34% of theory) of the title compound which was used without further characterization in the next step. The resulting reaction mixture the organic phase was washed with aqueous saturated sodium bicarbonate solution After drying over sodium sulphate the mixture was concentrated by evaporation the residue was purified by chromatography on silica gel (mobile phase: hexane/ethyl acetate gradient/1% triethylamine) Evaporation drying

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6.00 g (26.19 mmol) of (5-bromo-2-methylphenyl)acetic acid (EP 1791816 A1 and US 2006/29799 A1) were dissolved in 31.20 g (261.92 mmol) of thionyl chloride. The reaction mixture was stirred at 80° C. for two hours and then concentrated under reduced pressure. Drying under fine vacuum gave 6.29 g (97% of theory) of the title compound as a brownish oil. concentrated under reduced pressure Drying under fine vacuum