3-Boc-2,2-dimethyloxazolidine-4-carboxaldehyde, (S)-(-)- → (R)-4-[(1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-2-nitropropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

HRID 20420

Reaction equation

HRID 20420 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[C:19]([O:23][C:24]([N:26]1[C@H:30]([CH:31]=[O:32])[CH2:29][O:28][C:27]1([CH3:34])[CH3:33])=[O:25])([CH3:22])([CH3:21])[CH3:20].[F:35][C:36]1[CH:41]=[C:40]([CH2:42][CH2:43][N+:44]([O-:46])=[O:45])[CH:39]=[C:38]([F:47])[CH:37]=1>O1CCCC1>[C:19]([O:23][C:24]([N:26]1[C@@H:30]([C@@H:31]([OH:32])[C@@H:43]([N+:44]([O-:46])=[O:45])[CH2:42][C:40]2[CH:41]=[C:36]([F:35])[CH:37]=[C:38]([F:47])[CH:39]=2)[CH2:29][O:28][C:27]1([CH3:34])[CH3:33])=[O:25])([CH3:22])([CH3:21])[CH3:20]

Participants

5

Reactant 3

HCID 1798243-Boc-2,2-dimethyloxazolidine-4-carboxaldehyde, (S)-(-)-HCID 2724141Tetrabutylammonium FluorideHCID 552507531,3-Difluoro-5-(2-nitroethyl)benzene

Product 1

HCID 58972248(R)-4-[(1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-2-nitropropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl esterYield 37.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Add tetrabutylammonium fluoride in 5 minutes (50 mL, 50 mmol, 1.0 M solution in tetrahydrofuran) to a solution of (S)-4-formyl-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester (200 g, 873.362 mmol) and 1,3-difluoro-5-(2-nitroethyl)-benzene (164 g, 877.005 mmol) in tetrahydrofuran (1.2 L) at 8° C. Allow to warm to room temperature and stir for 14 hours. Partition between ethyl acetate (4 L) and saturated aqueous sodium chloride (1.5 L). Wash the organic layer with saturated aqueous ammonium chloride, saturated aqueous sodium chloride, water, dry (magnesium sulfate), filter and concentrate to give 379 g of a crude waxy pale orange solid. Recrystallize in dichloromethane/hexanes to give the title compound (137.15 g, 37.7%).

Workup

  1. customPartition between ethyl acetate (4 L) and saturated aqueous sodium chloride (1.5 L)
  2. washWash the organic layer with saturated aqueous ammonium chloride, saturated aqueous sodium chloride, water
  3. dry with materialdry (magnesium sulfate)
  4. filtrationfilter
  5. concentrationconcentrate
  6. customto give 379 g of a crude waxy pale orange solid
  7. customRecrystallize in dichloromethane/hexanes

Sources & evidence

ORD record
ord-74539357565a492c9ff90b62911522ae
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Linked notes

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