Sodium hydride → 6-{(SR)-1-[(3RS,4SR)-1-Benzyl-4-(4-cyano-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile

HRID 559290Notes

Reaction equation

HRID 559290 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([CH:13]([OH:15])[CH3:14])[CH:10]([C:16]2[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:27]1[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][N:28]=1>CN(C=O)C>[CH2:1]([N:8]1[CH2:9][CH:10]([C:16]2[CH:17]=[CH:18][C:19]([C:20]#[N:21])=[CH:22][CH:23]=2)[CH:11]([CH:13]([O:15][C:27]2[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][N:28]=2)[CH3:14])[CH2:12]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 669996874-[(3SR,4RS)-1-benzyl-4-((RS)-1-hydroxy-ethyl)-pyrrolidin-3-yl]-benzonitrile

Product 1

HCID 669996036-{(SR)-1-[(3RS,4SR)-1-Benzyl-4-(4-cyano-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrileYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 4-[(3SR,4RS)-1-benzyl-4-((SR)-1-hydroxy-ethyl)-pyrrolidin-3-yl]-benzonitrile (V-A-5) (0.65 g, 2.12 mmol) in DMF (40 mL) at RT was added NaH (55% purity, 0.10 g, 4.1 mmol). After 10 minutes, 6-chloro-nicotinonitrile (0.32 g, 2.33 mmol) was added. The reaction mixture was stirred over night at RT, filtered on celite and concentrated under vacuo. Extraction with EtOAc/aq.NH4Cl sat, followed by column chromatography (SiO2, EtOAc/H, 1:1) yielded 0.39 g (45%) of the title compound as a colorless oil. ES-MS m/e: 409.3 (M+H+).

Workup

  1. filtrationfiltered on celite
  2. concentrationconcentrated under vacuo
  3. extractionExtraction with EtOAc/aq

Sources & evidence

ORD record
ord-4e22381514374eab976f46fa2bb6a834
Source dataset
uspto-grants-2011_11
Patent number
US08063075B2

Reaction notes

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