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 the solution was chilled in a dry ice/acetone bath, triethylamine (3.06 mL) was added, followed by dropwise addition of methanesulfonyl chloride (1.70 mL) and stirring for 1 hour. Subsequently, water (40 mL) was added and the mixture was allowed to warm to room temperature. The dichloromethane layer was separated and the aqueous layer was extracted with dichloromethane (40 mL). The dichloromethane layers were combined, washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in N,N-dimethylformamide (120 mL), followed by the addition of tetrabutylammonium cyanide (5.53 g) and sodium cyanide (2.05 g) and stirring at 80° C. for 13 hours. Subsequently, the reaction mixture was concentrated under reduced pressure. Water (50 mL) was then added to the resulting residue and the mixture was extracted with diethyl ether (2×200 mL). The diethyl ether layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to give (3R,4S)-1-benzyl-4-methyl-3-pyrrolidinecarbonitrile as a brown oil (3.32 g).

1. temperatureWhile the solution was chilled in a dry ice/acetone bath
2. customThe dichloromethane layer was separated
3. extractionthe aqueous layer was extracted with dichloromethane (40 mL)
4. washwashed with water
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. dissolutionThe resulting residue was dissolved in N,N-dimethylformamide (120 mL)
8. additionfollowed by the addition of tetrabutylammonium cyanide (5.53 g) and sodium cyanide (2.05 g)
9. stirringstirring at 80° C. for 13 hours
10. concentrationSubsequently, the reaction mixture was concentrated under reduced pressure
11. additionWater (50 mL) was then added to the resulting residue
12. extractionthe mixture was extracted with diethyl ether (2×200 mL)
13. washwashed with saturated brine
14. dry with materialdried over anhydrous sodium sulfate
15. concentrationconcentrated under reduced pressure
16. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)

ORD record

ord-e7072eabcda142d98bffbe4bfac710c3

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08106072B2