Aluminium lithium hydride → (R)-1-[(3R,4S)-1-benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-ethanol

HRID 559298Notes

Reaction equation

HRID 559298 reaction equation
[CH2:1]([N:8]1[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([F:20])[CH:14]=2)[C@@H:10]([C:21](=[O:23])[CH3:22])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH2:1]([N:8]1[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([F:20])[CH:14]=2)[C@@H:10]([C@H:21]([OH:23])[CH3:22])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 669997021-[(3R,4S)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-ethanone

Product 1

HCID 66999243(R)-1-[(3R,4S)-1-benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-ethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-[(3R,4S)-1-benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-ethanone (260 mg, 0.78 mmol) in THF (10 mL) at 0° C. were added portion wise LiAlH4 (26 mg, 0.68 mmol). Stirring was continued for one hour, 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 (R)-1-[(3R,4S)-1-benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-ethanol (IV-B-9) 101 mg (38%) as a white solid ES-MS m/e: 334.2 (M+H+) and (S)-1-[(3R,4S)-1-benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-ethanol (IV-A-9) 80 mg (30%) as a white solid ES-MS m/e: 334.2 (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-e89acb2975bb4787a065d3039fb863a8
Source dataset
uspto-grants-2011_11
Patent number
US08063075B2

Reaction notes

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