Sodium hydride → (2R,4R)-2-[(4S,5S)-3-Acetyl-4-(3,5-difluoro-benzyl)-2,2-dimethyl-oxazolidin-5-yl]-4-(3-trifluoromethoxy-benzyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 732611Notes

Reaction equation

HRID 732611 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:14][C@H:13]([OH:15])[CH2:12][C@@H:11]1[C@H:16]1[O:20][C:19]([CH3:22])([CH3:21])[N:18]([C:23](=[O:25])[CH3:24])[C@H:17]1[CH2:26][C:27]1[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([F:34])[CH:28]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Br[CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([O:43][C:44]([F:47])([F:46])[F:45])[CH:38]=1>CN(C)C=O>[C:3]([O:7][C:8]([N:10]1[CH2:14][C@H:13]([O:15][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([O:43][C:44]([F:45])([F:46])[F:47])[CH:38]=2)[CH2:12][C@@H:11]1[C@H:16]1[O:20][C:19]([CH3:21])([CH3:22])[N:18]([C:23](=[O:25])[CH3:24])[C@H:17]1[CH2:26][C:27]1[CH:28]=[C:29]([F:34])[CH:30]=[C:31]([F:33])[CH:32]=1)=[O:9])([CH3:4])([CH3:5])[CH3:6]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 7371761-(Bromomethyl)-3-(trifluoromethoxy)benzeneHCID 68814386(2R,4R)-2-[(4S,5S)-3-Acetyl-4-(3,5-difluorobenzyl)-2,2-dimethyloxazolidin-5-yl]-4-hydroxypyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68817268(2R,4R)-2-[(4S,5S)-3-Acetyl-4-(3,5-difluoro-benzyl)-2,2-dimethyl-oxazolidin-5-yl]-4-(3-trifluoromethoxy-benzyloxy)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 102%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Add 95% sodium hydride (0.008 g, 0.33 mmol) over 5 minutes to a solution of (2R,4R)-2-[(4S,5S)-3-acetyl-4-(3,5-difluorobenzyl)-2,2-dimethyloxazolidin-5-yl]-4-hydroxypyrrolidine-1-carboxylic acid tert-butyl ester (0.101 g, 0.22 mmol) and 1-bromomethyl-3-trifluoromethoxy-benzene (0.054 mL, 0.333 mmol) in N,N-dimethylformamide (1 mL). Stir 1 hour and partition with ethyl acetate and water, wash with saturated aqueous sodium chloride, dry with magnesium sulfate and purify on silica gel with ethyl acetate/hexane mixtures to give the desired compound as a foam (0.141 g, 100%).

Workup

  1. custompartition with ethyl acetate and water
  2. washwash with saturated aqueous sodium chloride
  3. dry with materialdry with magnesium sulfate
  4. custompurify on silica gel with ethyl acetate/hexane

Sources & evidence

ORD record
ord-ced9cc19322d4cd09ef20a1962c0a540
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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