Sodium Iodide → (R)-4-[(1S,2S)-2-Acetylamino-1-benzyloxy-3-(3,5-difluoro-phenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

HRID 20335Notes

Reaction equation

HRID 20335 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C@@H:13]([OH:28])[C@@H:14]([NH:24][C:25](=[O:27])[CH3:26])[CH2:15][C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[CH:17]=2)[CH2:11][O:10][C:9]1([CH3:30])[CH3:29])=[O:7])([CH3:4])([CH3:3])[CH3:2].[I-].[Na+].[CH2:33](Br)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C@@H:13]([O:28][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C@@H:14]([NH:24][C:25](=[O:27])[CH3:26])[CH2:15][C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[CH:17]=2)[CH2:11][O:10][C:9]1([CH3:30])[CH3:29])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 7498Benzyl BromideHCID 68562048(R)-4-[(1S,2S)-2-Acetylamino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

Product 1

HCID 68561152(R)-4-[(1S,2S)-2-Acetylamino-1-benzyloxy-3-(3,5-difluoro-phenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl esterYield 85.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Suspend (R)-4-[(1S,2S)-2-acetylamino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester (4.78 g, 11.2 mmol) in dry tetrahydrofuran (115 ml) under a nitrogen atmosphere and add sodium hydride NaH (60% weight dispersion in mineral oil, 1.17 g, 29.3 mmol). Stir the resulting mixture for 30 minutes and then add sequentially sodium iodide (600 mg, 4.0 mmol) and benzyl bromide (2.7 mL, 22.7 mmol). Stir the resulting mixture for 2.5 hours and then quench by the addition of a 1:1 mixture of saturated aqueous ammonium chloride and saturated aqueous sodium chloride. Dilute the resulting mixture with ethyl acetate and discard the aqueous phase. Wash the organic phase with saturated aqueous sodium chloride, dry over magnesium sulfate, filter, concentrate and purify (silica gel chromatography, eluting with 0:100 to 40:60 ethyl acetate:hexanes) to give the desired compound as a white foam (4.96 g, 85%).

Workup

  1. stirringStir the resulting mixture for 2.5 hours
  2. customquench by the addition of a 1:1 mixture of saturated aqueous ammonium chloride and saturated aqueous sodium chloride
  3. additionDilute the resulting mixture with ethyl acetate
  4. washWash the organic phase with saturated aqueous sodium chloride
  5. dry with materialdry over magnesium sulfate
  6. filtrationfilter
  7. concentrationconcentrate
  8. custompurify
  9. wash(silica gel chromatography, eluting with 0:100 to 40:60 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-9134fb0a44d14ed7b7ac6d0e074d8dd3
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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