Chlorotrimethylsilane → Perindopril Erbumine

関与物質

反応条件

反応手順

To (2S,3aS,7aS)-octahydroindole-2-carboxylic acid (7.44 g) in dichloromethane (80 mL) at 20-25° C., trimethylchlorosilane (5.84 mL) and triethylamine (6.4 mL) were added and it was stirred at 20-25° C. for two hours. After two hours triethylamine (5.54 mL) was added, the suspension was cooled to −15° C., a suspension of N—((S)-1-carbetoxybutyl)-L-alanylchloride hydrochloride (11 g) in dichloromethane (80 mL), cooled to −15° C., was poured thereto and the stirring was continued at a temperature from 0° C. to −5° C. for two hours. The reaction solution was heated to 0° C., the precipitated triethylamine hydrochloride was filtered off and washed with dichloromethane (20 mL), water (66 mL) in which NaOH (1.6 g) had been dissolved was added to the filtrate and the pH was adjusted to 4.2 with a 20% NaOH solution. The organic phase was separated and the aqueous layer was washed two more times with dichloromethane (40 mL). The combined dichloromethane layers were evaporated, the residue was dissolved in isopropyl acetate (250 mL), the undissolved part was filtered off, and t-butylamine (4.4 mL) was added to the filtrate. The precipitated crystals were dissolved at the boiling point of the solution, the clear solution was cooled to 10-20° C. and it was continued with stirring for two hours. After two hours, the precipitated crystals were filtered off, washed with isopropyl acetate (30 mL) and dried at 35-40° C. in an air dryer. 15.3 g of perindopril erbumine in alpha form with a purity of more than 99% were obtained; the content of single impurities was not above 0.1%.

情報源と証拠