Lithium borohydride → 4-[(3SR,4RS)-1-benzyl-4-((RS)-1-hydroxy-ethyl)-pyrrolidin-3-yl]-benzonitrile

HRID 559289Notes

Reaction equation

HRID 559289 reaction equation
[C:1]([CH:4]1[CH2:8][N:7]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:6][CH:5]1[C:16]1[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=1)(=[O:3])[CH3:2].[Li+].[BH4-]>CO>[CH2:9]([N:7]1[CH2:8][CH:4]([CH:1]([OH:3])[CH3:2])[CH:5]([C:16]2[CH:17]=[CH:18][C:19]([C:20]#[N:21])=[CH:22][CH:23]=2)[CH2:6]1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 669991814-((3SR,4RS)-4-Acetyl-1-benzyl-pyrrolidin-3-yl)-benzonitrile

Product 1

HCID 669996874-[(3SR,4RS)-1-benzyl-4-((RS)-1-hydroxy-ethyl)-pyrrolidin-3-yl]-benzonitrile

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 4-((3SR,4RS)-4-acetyl-1-benzyl-pyrrolidin-3-yl)-benzonitrile (IV-5) (IV-5) (6.30 g, 20.7 mmol) in MeOH (300 mL) at RT were added portion wise LiBH4 (9.49 g, 0.43 mol). Stirring was continued for overnight, and the reaction mixture was carefully quenched by addition of aq. NH4Cl, concentrated under vacuo and the product extracted with EtOAC. The combined organic phases were dried on Na2SO4 and concentrated under vacuo. The two diastereoisomeres were separated by column chromatography (SiO2, EtOAc/H, 1:1) to yield 4-[(3SR,4RS)-1-benzyl-4-((RS)-1-hydroxy-ethyl)-pyrrolidin-3-yl]-benzonitrile (V-B-5) 1.35 g (21%) as a colorless oil ES-MS m/e: 307.2 (M+H+) and 4-[(3SR,4RS)-1-benzyl-4-((SR)-1-hydroxy-ethyl)-pyrrolidin-3-yl]-benzonitrile (V-A-5) 1.30 g (20%) as a colorless oil ES-MS m/e: 307.2 (M+H+).

Workup

  1. customthe reaction mixture was carefully quenched by addition of aq. NH4Cl
  2. concentrationconcentrated under vacuo
  3. extractionthe product extracted with EtOAC
  4. customThe combined organic phases were dried on Na2SO4
  5. concentrationconcentrated under vacuo
  6. customThe two diastereoisomeres were separated by column chromatography (SiO2, EtOAc/H, 1:1)

Sources & evidence

ORD record
ord-f0d361a4f53b41e1ae14414402a59250
Source dataset
uspto-grants-2011_11
Patent number
US08063075B2

Reaction notes

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