Aluminium lithium hydride → (3R,4S)-1-Benzyl-4-(3,4-difluoro-phenyl)-pyrrolidine-3-carbaldehyde

HRID 906942Notes

Reaction equation

HRID 906942 reaction equation
CON(C)[C:4]([C@@H:6]1[C@@H:10]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([F:18])[CH:12]=2)[CH2:9][N:8]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:7]1)=[O:5].[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[CH2:19]([N:8]1[CH2:9][C@H:10]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([F:18])[CH:12]=2)[C@@H:6]([CH:4]=[O:5])[CH2:7]1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 86627624(3R,4S)-1-Benzyl-4-(3,4-difluoro-phenyl)-pyrrolidine-3-carboxylic acid methoxy-methyl-amide

Product 1

HCID 86627625(3R,4S)-1-Benzyl-4-(3,4-difluoro-phenyl)-pyrrolidine-3-carbaldehydeYield 99.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3R,4S)-1-benzyl-4-(3,4-difluoro-phenyl)-pyrrolidine-3-carboxylic acid methoxy-methyl-amide 3.24 g (9 mmol) dissolved in THF (60 mL) was added 9 mL (9 mmol) of lithiumaluminiumhydride (1.0M in THF) dropwise at 0° C. and stirred for one hour. The reaction was quenched by aq. ammonium chloride solution and extracted with ethylacetate twice. The combined organic layers were dired on anhydrous sodium sulfate and concentrated in vaccuo. The residue was purified by silica gel column chromatography eluted by a mixture of heptane and ethyl acetate (3:2) yielding 2.7 g (99%) of the title compound as a light yellow oil. ES-MS m/e: 302.1 (M+H+).

Workup

  1. customThe reaction was quenched by aq. ammonium chloride solution
  2. extractionextracted with ethylacetate twice
  3. concentrationconcentrated in vaccuo
  4. customThe residue was purified by silica gel column chromatography
  5. washeluted by a mixture of heptane and ethyl acetate (3:2)

Sources & evidence

ORD record
ord-df20ae8534604560b7e344a6a87a9282
Source dataset
uspto-grants-2011_09
Patent number
US08012998B2

Reaction notes

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