反应详情

Cool a mixture of ethyl acetate (214 mL) and ethanol (87.6 mL, 1.51 mol) to 0° C., and then add acetyl chloride (97.4 mL, 1.37 mol) in a dropwise fashion. Stir the mixture for 30 minutes while allowing it to warm to room temperature. Add a solution of tert-butyl (3R)-3-[[(1S)-1-(4-methoxycarbonylphenyl)ethyl]carbamoyl]-3,4-dihydro-1H-isoquinoline-2-carboxylate (60 g, 137 mmol) in ethyl acetate (480 mL), and then stir the resulting mixture at 40° C. overnight. Cool the mixture to room temperature, then isolate the resulting precipitate by filtration, and dry under reduced pressure. Add water (300 mL) to the solid, and then add a 32% aqueous ammonia solution until the pH of the mixture reaches 10. Isolate the suspended solids by filtration, then dry them in a vacuum oven at 45° C. overnight to furnish the title compound as a white solid (44 g, 95% yield). Mass spectrum (m/z): 339 ([M+H]+), 677 ([2M+H]+), 699 ([2M+Na]+).

1. temperatureCool
2. stirringstir the resulting mixture at 40° C. overnight
3. temperatureCool the mixture to room temperature
4. customisolate the resulting precipitate
5. filtrationby filtration
6. customdry under reduced pressure
7. additionAdd water (300 mL) to the solid, and then add a 32% aqueous ammonia solution until the pH of the mixture
8. customIsolate the suspended solids
9. filtrationby filtration
10. customdry them in a vacuum oven at 45° C. overnight