Aluminium lithium hydride → (2S,4S)-2-Hydroxymethyl-4-phenyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 238987Notes

Reaction equation

HRID 238987 reaction equation
C[O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:7][N:6]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].O1CCCC1.O>O1CCCC1>[C:19]([O:18][C:16]([N:6]1[CH2:7][C@H:8]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:9][C@H:5]1[CH2:3][OH:2])=[O:17])([CH3:22])([CH3:21])[CH3:20]

Participants

5

Reactant 3

HCID 21226445Aluminium lithium hydrideHCID 21881883Oxolane--water (1/1)HCID 580029141-(tert-Butyl) 2-methyl (2S,4S)-4-phenylpyrrolidine-1,2-dicarboxylate

Product 1

HCID 58002916(2S,4S)-2-Hydroxymethyl-4-phenyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

4.2 g of (2S,4S)-4-Phenyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (13.75 mmol) in 30 ml tetrahydrofuran were slowly added to a suspension of 0.27 g of lithium aluminium hydride in 50 ml tetrahydrofurane. Stirring was continued for 5 h at 0-5° C. and for 14 h at room temperature. For workup, a mixture of tetrahydrofurane/water (1:1) was slowly added to the reaction mixture at 0° C. The solvent was then evaporated under reduced pressure, water was added and the pH was adjusted to about 5 with 20% aqueous citric acid. The aqueous phase was extracted four times with ethyl acetate, the organic layers were combined, dried over magnesium sulphate, filtered, and the solvent was removed under reduced pressure to yield 3.85 of product.

Workup

  1. additionwas slowly added to the reaction mixture at 0° C
  2. customThe solvent was then evaporated under reduced pressure, water
  3. additionwas added
  4. extractionThe aqueous phase was extracted four times with ethyl acetate
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. customto yield 3.85 of product

Sources & evidence

ORD record
ord-d6f426645a6842ef9bac8bb00f3b9f0c
Source dataset
uspto-grants-2014_02
Patent number
US08642642B2

Reaction notes

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