Acetone → (2R,4R)-2-[(4S,5S)-3-Acetyl-4-(3,5-difluorobenzyl)-2,2-dimethyloxazolidin-5-yl]-4-(4-methoxy-benzyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 732601Notes

Reaction equation

HRID 732601 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH2:10][C@@H:9]1[C@@H:23]([OH:38])[C@@H:24]([NH:34][C:35](=[O:37])[CH3:36])[CH2:25][C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([F:33])[CH:27]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:39][C:40]([CH3:42])=O.COC(C)=C>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=2)[CH2:10][C@@H:9]1[C@H:23]1[O:38][C:40]([CH3:42])([CH3:39])[N:34]([C:35](=[O:37])[CH3:36])[C@H:24]1[CH2:25][C:26]1[CH:27]=[C:28]([F:33])[CH:29]=[C:30]([F:32])[CH:31]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 180AcetoneHCID 83002-MethoxypropeneHCID 68814707(2R,4R)-2-[(1S,2S)-2-acetylamino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-4-(4-methoxy-benzyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68816295(2R,4R)-2-[(4S,5S)-3-Acetyl-4-(3,5-difluorobenzyl)-2,2-dimethyloxazolidin-5-yl]-4-(4-methoxy-benzyloxy)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 607.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add to a solution of (2R,4R)-2-[(1S,2S)-2-acetylamino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-4-(4-methoxy-benzyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (5.64 g, 10.55 mmol) in dichloromethane (25 mL) and acetone (25 mL) p-toluene sulfonic acid pyridine salt (0.245 g, 1 mmol) and 2-methoxy propene (4.6 mL, 49 mmol). Stir 60 min and concentrate. Dissolve in ethyl acetate and wash with saturated aqueous sodium bicarbonate, saturated aqueous sodium chloride, dry (magnesium sulfate) and purify (silica gel chromatography, eluting with hexanes/ethyl acetate mixtures) to give the title compound as a foam (3.49 g, 61%).

Workup

  1. concentrationconcentrate
  2. dissolutionDissolve in ethyl acetate
  3. washwash with saturated aqueous sodium bicarbonate, saturated aqueous sodium chloride
  4. dry with materialdry (magnesium sulfate)
  5. custompurify
  6. wash(silica gel chromatography, eluting with hexanes/ethyl acetate mixtures)

Sources & evidence

ORD record
ord-5637c2c7aed64c0eaf3b5a657d5f73cc
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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