Water → (3R,4S)-1-Benzyl-4-methylpyrrolidine-3-carbonitrile

(3R,4S)-1-Benzyl-3-hydroxy-4-methylpyrrolidine (4.00 g) was dissolved in dichloromethane (40 mL). While this solution was cooled on a dry ice/acetone bath, triethylamine (3.06 mL) was added. Methanesulfonyl chloride (1.70 mL) was then added dropwise and the mixture was further stirred for 1 hour. Following addition of water (40 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 (40 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 N,N-dimethylformamide (120 mL). To this solution, tetrabutylammonium cyanide (5.53 g) and sodium cyanide (2.05 g) were added and the mixture was stirred at 80° C. for 13 hours. Subsequently, the reaction mixture was concentrated under reduced pressure and water (50 mL) was added to the resulting residue. The mixture was extracted with diethyl ether (2×200 mL). The diethyl ether extracts were combined and the combined extract was washed with a saturated aqueous solution of sodium chloride, followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was purified on a silica gel column (hexane: ethyl acetate=4:1) to give 3.32 g of (3R,4S)-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 (40 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 N,N-dimethylformamide (120 mL)
8. additionTo this solution, tetrabutylammonium cyanide (5.53 g) and sodium cyanide (2.05 g) were added
9. stirringthe mixture was stirred at 80° C. for 13 hours
10. concentrationSubsequently, the reaction mixture was concentrated under reduced pressure and water (50 mL)
11. additionwas added to the resulting residue
12. extractionThe mixture was extracted with diethyl ether (2×200 mL)
13. extractionthe combined extract
14. washwas washed with a saturated aqueous solution of sodium chloride
15. dry with materialby drying over anhydrous sodium sulfate and concentration under reduced pressure
16. customThe resulting residue was purified on a silica gel column (hexane: ethyl acetate=4:1)

ORD record

ord-5c3f7ff692714eb39ffab8a95e36dc7f

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07153851B2