反应详情

A mixed solution obtained by mixing 3.9 g of 79% pure (S)-1-benzyl-3-(1-cyano-1,1-diphenylmethyl)-pyrrolidine with 3.1 ml of ethanol and adding dropwise 446 mg of 97% sulfuric acid thereto with cooling on an ice-water bath was charged, together with 158 mg of moist 5% palladium-carbon (water content 52% by weight), into an autoclave, hydrogen was introduced thereinto and the autoclave was heated to raise the temperature to 60 and the pressure to 203 kPa, and the reaction was allowed to proceed for 3.5 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and depressurized. The reaction mixture was taken out, the catalyst was filtered off, the filtrate obtained was concentrated under reduced pressure, toluene and water were added to the thus-obtained oily concentrate, and the pH was adjusted to 13 by adding dropwise 30% aqueous sodium hydroxide with stirring on an ice-water bath. The toluene layer was recovered, the aqueous layer was further extracted with toluene, and the toluene layers were combined, washed with a saturated aqueous solution of sodium chloride, dried with anhydrous sodium sulfate and, after filtration, concentrated under reduced pressure, to give an oil. This was purified by silica gel column chromatography using, as an eluant, dichloromethane containing methanol (0% to 10%). Main fractions containing the product were combined and concentrated under vacuum to give (S)-3-(1-cyano-1,1-diphenylmethyl)-pyrrolidine in a yield of 84 mole percent.

1. customA mixed solution obtained
2. temperaturewith cooling on an ice-water bath
3. additionwas introduced
4. temperaturethe autoclave was heated
5. temperatureto raise the temperature to 60
6. customAfter completion of the reaction
7. filtrationthe catalyst was filtered off
8. customthe filtrate obtained
9. concentrationwas concentrated under reduced pressure, toluene and water
10. additionwere added to the thus-obtained oily concentrate
11. additionby adding dropwise 30% aqueous sodium hydroxide
12. customThe toluene layer was recovered
13. extractionthe aqueous layer was further extracted with toluene
14. washwashed with a saturated aqueous solution of sodium chloride
15. dry with materialdried with anhydrous sodium sulfate
16. filtrationafter filtration
17. concentrationconcentrated under reduced pressure
18. customto give an oil
19. customThis was purified by silica gel column chromatography
20. additiondichloromethane containing methanol (0% to 10%)
21. additionMain fractions containing the product
22. concentrationconcentrated under vacuum