Water → cis-1-Benzyl-4-methyl-3-pyrrolidinecarbonitrile

c is-1-Benzyl-3-hydroxy-4-methylpyrrolidine (6.81 g) was dissolved in dichloromethane (70 mL). While this solution was cooled on a dry ice/acetone bath, triethylamine (5.21 mL) was added. Methanesulfonyl chloride (2.89 mL) was then added dropwise and the mixture was further stirred for 1 hour. Following addition of water (50 mL), the temperature of the mixture was allowed to rise to room temperature and the dichloromethane layer was separated. The aqueous layer was extracted with dichloromethane (50 mL) and the extract was combined with the dichloromethane layer. The combined dichloromethane layer was then washed with water, followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was dissolved in acetonitrile (180 mL). To this solution, tetrabutylammonium cyanide (23.9 g) was added and the mixture was refluxed for 7 hours while heated. Subsequently, the reaction mixture was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate (300 mL). The solution was washed with water, was dried over anhydrous sodium sulfate, and was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (hexane:ethyl acetate=1:1) to give 4.61 g of cis-1-benzyl-4-methyl-3-pyrrolidinecarbonitrile as a brown oil.

1. temperatureWhile this solution was cooled on a dry ice/acetone bath
2. customto rise to room temperature
3. customthe dichloromethane layer was separated
4. extractionThe aqueous layer was extracted with dichloromethane (50 mL)
5. washThe combined dichloromethane layer was then washed with water
6. dry with materialby drying over anhydrous sodium sulfate and concentration under reduced pressure
7. dissolutionThe resulting residue was dissolved in acetonitrile (180 mL)
8. additionTo this solution, tetrabutylammonium cyanide (23.9 g) was added
9. temperaturethe mixture was refluxed for 7 hours
10. temperaturewhile heated
11. concentrationSubsequently, the reaction mixture was concentrated under reduced pressure
12. dissolutionthe resulting residue was dissolved in ethyl acetate (300 mL)
13. washThe solution was washed with water
14. dry with materialwas dried over anhydrous sodium sulfate
15. concentrationwas concentrated under reduced pressure
16. customThe resulting residue was purified on a silica gel column (hexane:ethyl acetate=1:1)

ORD record

ord-89f4386f408c40d7a27f044db9990292

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07153851B2