Aluminium lithium hydride → (RS)-1-[(3RS,4SR)-4-(2,4-difluoro-phenyl)-pyrrolidin-3-yl]-ethanol

HRID 906905Notes

Reaction equation

HRID 906905 reaction equation
C([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[F:20])[CH:10]([C:21](=[O:23])[CH3:22])[CH2:9]1)C1C=CC=CC=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[F:20][C:14]1[CH:15]=[C:16]([F:19])[CH:17]=[CH:18][C:13]=1[CH:11]1[CH2:12][NH:8][CH2:9][CH:10]1[CH:21]([OH:23])[CH3:22]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 669992391-[(3RS,4SR)-1-Benzyl-4-(2,4-difluoro-phenyl)-pyrrolidin-3-yl]-ethanone

Product 1

HCID 66999146(RS)-1-[(3RS,4SR)-4-(2,4-difluoro-phenyl)-pyrrolidin-3-yl]-ethanolYield 53.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-[(3SR,4RS)-1-benzyl-4-(2,4-difluoro-phenyl)-pyrrolidin-3-yl]-ethanone (IX-14) (1.87 g, 5.92mmol) in THF (30 mL) at 0° C. were added portion wise LiAlH4 (0.19 g, 5.21 mol). 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 (SR)-1-[(3SR,4RS)-4-(2,4-difluoro-phenyl)-pyrrolidin-3-yl]-ethanol (X-B-14) 0.72 g (38%) as a white solid ES-MS m/e: 318.1 (M+H+) and (RS)-1-[(3SR,4RS)-4-(2,4-difluoro-phenyl)-pyrrolidin-3-yl]-ethanol (X-A-14) 0.374 g (19%) as a white solid ES-MS m/e: 318.1 (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-056b67d016eb4478810bb8c4abd3575e
Source dataset
uspto-grants-2011_09
Patent number
US08012998B2

Reaction notes

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