反应详情

Cis-4-hydroxy-D-proline 8 (10.0 g, 76.3 mmol) was dissolved in H2O (165 mL) containing NaHCO3 (16.0 g, 190 mmol). Benzyl chloroformate (12.5 mL, 15.0 g, 87.7 mmol) in toluene (40 mL) was added to this stirring solution at room temperature over 30 minutes using a dropping funnel. The reaction was stirred for 16 h. By this time, CO2 evolution had ceased, and the two phases were separated. Excess benzyl chloroformate was removed from the aqueous layer by washing with ether (3×50 mL). The aqueous phase was cooled in an ice bath and acidified to pH2 with concentrated HCl, causing precipitation of the oily product. This oil was extracted from the aqueous layer by repeated washings with ethyl acetate (5×50 mL). Further acidification of the aqueous layer produced no more precipitate, indicating the extraction was complete. The combined organic layers were washed with brine, dried (MgSO4), and concentrated to a colorless viscous oil, which crystallized upon standing at room temperature to provide 19.42 g (96%) of N-CBZ-cis-4-hydroxy-D-proline: mp 110°-111° C. (lit. 19 mp 110.5°-111.5° C.); [α]25d +24.4° (c 1.0, CHCl3) ]lit. 19 [α25D +26.3° (c 1.0, CHCl3)].

1. customthe two phases were separated
2. customExcess benzyl chloroformate was removed from the aqueous layer
3. washby washing with ether (3×50 mL)
4. temperatureThe aqueous phase was cooled in an ice bath
5. customprecipitation of the oily product
6. extractionThis oil was extracted from the aqueous layer by repeated washings with ethyl acetate (5×50 mL)
7. customFurther acidification of the aqueous layer produced no more precipitate
8. extractionthe extraction
9. washThe combined organic layers were washed with brine
10. dry with materialdried (MgSO4)
11. concentrationconcentrated to a colorless viscous oil, which
12. customcrystallized
13. customupon standing at room temperature