N-Boc-4,4-difluoro-L-proline methyl ester → tert-Butyl (2S)-4,4-difluoro-2-(hydroxymethyl)pyrrolidine-1-carboxylate
Reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C[O:8][C:9]([C@@H:11]1[CH2:15][C:14]([F:17])([F:16])[CH2:13][N:12]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=O>C1COCC1>[C:21]([O:20][C:18]([N:12]1[CH2:13][C:14]([F:16])([F:17])[CH2:15][C@H:11]1[CH2:9][OH:8])=[O:19])([CH3:24])([CH3:23])[CH3:22]Participants
Procedure
Lithium aluminium hydride (0.42 g, 0.011 mol) was added in portions to a solution of commercially available (S)-4,4-difluoro-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (1 g, 0.0037 mol) in dry THF (25 mL) att 0° C. and allowed to stir for 3 h. The reaction was monitored by TLC and after completion, it was quenched with sat. solution of Na2SO4 in cold condition. The reaction mixture was filtered through a Celite® plug. The filtrate was concentrated under reduced pressure using a rotary evaporator to give a crude material, which was purified via column chromatography (2-7% methanol:DCM, mesh Size-100-200 silica, diameter of column—2.5 cm, height of silica—approx. 6 inch) to give the desired (S)-4,4-difluoro-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.4 g) as a beige solid.
Workup
- customafter completion, it was quenched with sat. solution of Na2SO4 in cold condition
- filtrationThe reaction mixture was filtered through a Celite® plug
- concentrationThe filtrate was concentrated under reduced pressure
- customa rotary evaporator
- customto give a crude material, which
- customwas purified via column chromatography (2-7% methanol
Sources & evidence
- ORD record
- ord-4b474e3863964a2aba98626fe6127ba8
- Source dataset
- uspto-grants-2012_02
- Patent number
- US08124636B2
Reaction notes
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