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

HRID 424720Notes

Reaction equation

HRID 424720 reaction equation
[CH2:1]([N:8]1[CH2:12][C@H:11]([CH3:13])[C@H:10](O)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:15]([N:17](CC)CC)C.CS(Cl)(=O)=O.O>ClCCl>[CH2:1]([N:8]1[CH2:12][C@H:11]([CH3:13])[C@H:10]([C:15]#[N:17])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 54129200(3S,4S)-1-benzyl-4-methylpyrrolidin-3-ol

Product 1

HCID 66704969cis-1-Benzyl-4-methyl-3-pyrrolidinecarbonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

cis-1-Benzyl-3-hydroxy-4-methylpyrrolidine (6.81 g) was dissolved in dichloromethane (70 mL). While the solution was chilled in a dry ice/acetone bath, triethylamine (5.21 mL) was added, followed by dropwise addition of methanesulfonyl chloride (2.89 mL) and stirring for 1 hour. Subsequently, water (50 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 (50 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 acetonitrile (180 mL). To this solution, tetrabutylammonium cyanide (23.9 g) was added and the mixture was refluxed for 7 hours. Subsequently, the reaction mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate (300 mL). This solution was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was then purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give cis-1-benzyl-4-methyl-3-pyrrolidinecarbonitrile as a brown oil (4.61 g).

Workup

  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 (50 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 acetonitrile (180 mL)
  8. additionTo this solution, tetrabutylammonium cyanide (23.9 g) was added
  9. temperaturethe mixture was refluxed for 7 hours
  10. concentrationSubsequently, the reaction mixture was concentrated under reduced pressure
  11. dissolutionthe residue was dissolved in ethyl acetate (300 mL)
  12. washThis solution was washed with water
  13. dry with materialdried over anhydrous sodium sulfate
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was then purified by silica gel column chromatography (hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-1c17c7f708b14d36912640de9c196f31
Source dataset
uspto-grants-2012_01
Patent number
US08106072B2

Reaction notes

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