2-Methoxypropene → (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 732593Notes

Reaction equation

HRID 732593 reaction equation
N1C=C[CH:4]=[CH:3][CH:2]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.COC(C)=C.[C:23]([O:27][C:28]([N:30]1[CH2:34][C@H:33]([O:35][CH2:36][C:37]2[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=2)[CH2:32][C@@H:31]1[C@@H:45]([OH:60])[C@@H:46]([NH:56][C:57](=[O:59])[CH3:58])[CH2:47][C:48]1[CH:53]=[C:52]([F:54])[CH:51]=[C:50]([F:55])[CH:49]=1)=[O:29])([CH3:26])([CH3:25])[CH3:24]>ClCCl.CC(C)=O>[C:23]([O:27][C:28]([N:30]1[CH2:34][C@H:33]([O:35][CH2:36][C:37]2[CH:38]=[CH:39][C:40]([O:43][CH3:44])=[CH:41][CH:42]=2)[CH2:32][C@@H:31]1[C@H:45]1[O:60][C:3]([CH3:4])([CH3:2])[N:56]([C:57](=[O:59])[CH3:58])[C@H:46]1[CH2:47][C:48]1[CH:49]=[C:50]([F:55])[CH:51]=[C:52]([F:54])[CH:53]=1)=[O:29])([CH3:26])([CH3:24])[CH3:25]

Participants

6

Reactant 3

HCID 83002-MethoxypropeneHCID 161440Pyridine 4-methylbenzene-1-sulfonateHCID 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 2

HCID 180AcetoneSolventHCID 6344DichloromethaneSolvent

Procedure

Add p-toluene sulfonic acid pyridine salt (0.245 g, 1 mmol) and 2-methoxypropene (4.6 mL, 49 mmol) 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). Stir 60 min and concentrate under reduced pressure. Dissolve residue in ethyl acetate and wash with saturated aqueous sodium bicarbonate, saturated aqueous sodium chloride, dry magnesium sulfate and purify on silica gel with hexanes/ethyl acetate mixtures to give the desired compound as a foam (3.49 g, 61%).

Workup

  1. concentrationconcentrate under reduced pressure
  2. washDissolve residue in ethyl acetate and wash with saturated aqueous sodium bicarbonate, saturated aqueous sodium chloride, dry magnesium sulfate
  3. custompurify on silica gel with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-07a5b93d69dd48268e17949fca0efc3a
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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