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

HRID 20421Notes

Reaction equation

HRID 20421 reaction equation
[CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:15]([O:19][C:20]([N:22]1[C@@H:26]([C@@H:27]([OH:39])[C@@H:28]([NH2:38])[CH2:29][C:30]2[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([F:37])[CH:31]=2)[CH2:25][O:24][C:23]1([CH3:41])[CH3:40])=[O:21])([CH3:18])([CH3:17])[CH3:16]>C(#N)C.C(OCC)(=O)C>[C:15]([O:19][C:20]([N:22]1[C@@H:26]([C@@H:27]([OH:39])[C@@H:28]([N:38]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:29][C:30]2[CH:31]=[C:32]([F:37])[CH:33]=[C:34]([F:36])[CH:35]=2)[CH2:25][O:24][C:23]1([CH3:41])[CH3:40])=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 68562294(R)-4-[(1S,2S)-2-Amino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

Product 1

HCID 68561796(R)-4-[(1S,2S)-2-Dibenzylamino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl esterYield 87%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

Add benzyl bromide (75 mL, 630.55 mmol) to a suspension of potassium carbonate (85 g, 615.006 mmol) and (R)-4-[(1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester (80 g, 207.25 mmol) in acetonitrile (900 mL). Heat to reflux for 16 hours, cool to room temperature, and dilute with ethyl acetate (2 L). Wash with ammonium chloride (1.5 L), saturated aqueous sodium chloride (1.5 L), dry (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 5:95 to 20:80 ethyl acetate:hexanes) to give the desired compound as a white solid (102.1 g, 87%).

Workup

  1. temperatureHeat
  2. temperatureto reflux for 16 hours
  3. washWash with ammonium chloride (1.5 L), saturated aqueous sodium chloride (1.5 L)
  4. dry with materialdry (magnesium sulfate)
  5. filtrationfilter
  6. concentrationconcentrate
  7. custompurify
  8. wash(silica gel chromatography, eluting with 5:95 to 20:80 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-7ab923d931b14c908f4567a31b229555
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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