反应详情

温度

0 °C

A solution of Boc-D-Cha-OH (50.4 g, 185 mmol) in dichloromethane (360 mL) was cooled to 0° C. and N-hydroxysuccinimide (22.3 g, 194 mmol) was added. Then 1,3-dicyclohexylcarbodiimide (39.0 g, 189 mmol) was added in two portions as a solution in dichloromethane (90 mL). After stirring for 3 h at 0° C., L-Pro-OH (27.6 g, 240 mmol) and N,N-diisopropylethylamine (30.9 g, 239 mmol) were added. After stirring an additional 3 h between 0° C. and 10° C., the mixture was filtered over diatomaceous earth. The filter cake was rinsed with dichloromethane (100 mL); then the combined filtrates were concentrated in vacuo. The residual oil was partitioned between ethyl acetate (100 mL) and 0.625 M aqueous NaHCO3 (320 mL). The layers were separated, and the organic phase was washed with 0.625 M aq. NaHCO3 (80 mL). The combined bicarbonate extracts were then washed with ethyl acetate (100 mL). The aqueous phase was then stirred with ethyl acetate (300 mL) and acidified with 12 N HCl (approximately 37 mL). The layers were separated and the acidic aqueous phase was extracted with ethyl acetate (100 mL). The combined ethyl acetate extracts were concentrated in vacuo. The residue was slurried with a minimal amount of ethyl acetate, filtered, washed again with ethyl acetate and dried to give 50.1 g (73%) of white powder.

1. stirringAfter stirring an additional 3 h between 0° C. and 10° C.
2. filtrationthe mixture was filtered over diatomaceous earth
3. washThe filter cake was rinsed with dichloromethane (100 mL)
4. concentrationthen the combined filtrates were concentrated in vacuo
5. customThe residual oil was partitioned between ethyl acetate (100 mL) and 0.625 M aqueous NaHCO3 (320 mL)
6. customThe layers were separated
7. washthe organic phase was washed with 0.625 M aq. NaHCO3 (80 mL)
8. washThe combined bicarbonate extracts were then washed with ethyl acetate (100 mL)
9. stirringThe aqueous phase was then stirred with ethyl acetate (300 mL)
10. customThe layers were separated
11. extractionthe acidic aqueous phase was extracted with ethyl acetate (100 mL)
12. concentrationThe combined ethyl acetate extracts were concentrated in vacuo
13. filtrationfiltered
14. washwashed again with ethyl acetate
15. customdried