Sodium Hydroxide → (R)-1-(1-Benzylpyrrolidin-3-YL)cyclopropanamine

HRID 2099531Notes

Reaction equation

HRID 2099531 reaction equation
[C:1]([C@@H:3]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4]1)#[N:2].[CH2:15]([Mg]Br)[CH3:16].[OH-].[Na+]>O1CCCC1.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4]>[NH2:2][C:1]1([C@@H:3]2[CH2:7][CH2:6][N:5]([CH2:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH2:4]2)[CH2:16][CH2:15]1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 1515497(R)-1-Benzyl-3-pyrrolidinecarbonitrileHCID 178418443HCID 178418443, compound

Product 1

HCID 11171961(R)-1-(1-Benzylpyrrolidin-3-YL)cyclopropanamine

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

(3R)-3-Cyano-1-benzylpyrrolidine (1.40 g) was dissolved in tetrahydrofuran (21.0 mL) under an argon atmosphere. Titanium(IV) tetraisopropoxide (2.40 mL) and ethylmagnesium bromide (5.00 mL, 3 mol/L solution in ether) were added to the solution at room temperature. After 0.5 h, trifluoroboron-diethyl ether complex (1.90 mL) was added dropwise to the mixture, and the resultant mixture was stirred at room temperature. After 4 h, 2 mol/L aqueous sodium hydroxide (30 mL) was added to the reaction mixture, followed by stirring for 0.25 hours. The product that precipitated was collected through filtration and then extracted. The formed aqueous layer was again extracted with ethyl acetate, and the organic layers were combined together, washed with saturated brine, and dried over sodium sulfate. The drying agent was removed through filtration, and the filtrate was concentrated under reduced pressure, to thereby the target compound as a crude product (1.65 g).

Workup

  1. additiontrifluoroboron-diethyl ether complex (1.90 mL) was added dropwise to the mixture
  2. waitAfter 4 h
  3. customThe product that precipitated
  4. filtrationwas collected through filtration
  5. extractionextracted
  6. extractionThe formed aqueous layer was again extracted with ethyl acetate
  7. washwashed with saturated brine
  8. dry with materialdried over sodium sulfate
  9. customThe drying agent was removed through filtration
  10. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-a89a8175b51246f8b3c8c42d6e736f8b
Source dataset
uspto-grants-2009_08
Patent number
US07569599B2

Reaction notes

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