Benzyl Bromide → (R)-4-[(1S,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

HRID 20422Notes

Reaction equation

HRID 20422 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[C@@H:14]([C@@H:15]([OH:41])[C@@H:16]([N:26]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:17][C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=2)[CH2:13][O:12][C:11]1([CH3:43])[CH3:42])=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH2:44](Br)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.[Cl-].[NH4+]>CN(C)C=O>[C:3]([O:7][C:8]([N:10]1[C@@H:14]([C@@H:15]([O:41][CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[C@@H:16]([N:26]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:17][C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=2)[CH2:13][O:12][C:11]1([CH3:43])[CH3:42])=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 4

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 68561796(R)-4-[(1S,2S)-2-Dibenzylamino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

Product 1

HCID 68558039(R)-4-[(1S,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Add sodium hydride (4.4 g, 110 mmol, 60% in mineral oil) portionwise to a room temperature maintained solution of (R)-4-[(1S,2S)-2-dibenzylamino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester (50.5 g, 89.222 mmol) and benzyl bromide (22 mL, 184.96 mmol) in N,N-dimethylformamide (400 mL). Stir for 15 minutes and pour into saturated aqueous ammonium chloride. Extract with ethyl acetate, dry (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 2:98 to 4:96 ethyl acetate:hexanes) to give the title compound as a viscous oil that solidifies upon standing (48.5 g, 83%).

Workup

  1. extractionExtract with ethyl acetate
  2. dry with materialdry (magnesium sulfate)
  3. filtrationfilter
  4. concentrationconcentrate
  5. custompurify
  6. wash(silica gel chromatography, eluting with 2:98 to 4:96 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-253a4d6fd275467baf4d51ef47b51a8f
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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