反应详情

温度

22.5 °C

Trimethylchlorosilane (2.86 ml) and triethyl amine (3.08 ml) were added to (2S,3aS,7aS)-octahydroindole-2-carboxylic acid (3.72 g) in dichloromethane (60 ml) at 20-25° C. and stirred at 20-25° C. for two hours. After two hours triethyl amine (2.8 ml) was added, the suspension was cooled to −15° C., a suspension of N-((S)-1-carbethoxybutyl)-L-alanyl chloride hydrochloride (5.5 g) in dichloromethane (60 ml), which has been cooled to −15° C., was poured thereto and the stirring was continued at −15° C. for two hours. The reaction solution was heated to 0° C., brine (25 ml) with dissolved NaOH (0.8 g) was added, and the pH was adjusted to 4.2 with a 20% NaOH solution. The organic phase was separated and the aqueous layer was once more washed with dichloromethane (20 ml). The combined dichloromethane layers were evaporated, the residue was dissolved in ethyl acetate (100 ml), the undissolved part was filtered off and t-butylamine (2.2 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 the stirring was continued for two hours. After two hours the precipitated crystals were filtered off, washed with ethyl acetate (12 ml) and dried at 35-40° C. in an air drier.

1. temperaturethe suspension was cooled to −15° C.
2. temperaturehas been cooled to −15° C.
3. additionwas poured
4. waitthe stirring was continued at −15° C. for two hours
5. temperatureThe reaction solution was heated to 0° C.
6. customThe organic phase was separated
7. washthe aqueous layer was once more washed with dichloromethane (20 ml)
8. customThe combined dichloromethane layers were evaporated
9. dissolutionthe residue was dissolved in ethyl acetate (100 ml)
10. filtrationthe undissolved part was filtered off
11. additiont-butylamine (2.2 ml) was added to the filtrate
12. dissolutionThe precipitated crystals were dissolved at the boiling point of the solution
13. temperaturethe clear solution was cooled to 10-20° C.
14. waitthe stirring was continued for two hours
15. filtrationAfter two hours the precipitated crystals were filtered off
16. washwashed with ethyl acetate (12 ml)
17. customdried at 35-40° C. in an air drier