Sodium hydride → (2S,4R)-tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)-4-(3-fluoro-5-nitrophenoxy)pyrrolidine-1-carboxylate

HRID 495054

Reaction equation

HRID 495054 reaction equation
[Si:1]([O:8][CH2:9][C@@H:10]1[CH2:14][C@@H:13]([OH:15])[CH2:12][N:11]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].[F:25][C:26]1[CH:27]=[C:28]([N+:33]([O-:35])=[O:34])[CH:29]=[C:30](F)[CH:31]=1>CN(C=O)C>[Si:1]([O:8][CH2:9][C@@H:10]1[CH2:14][C@@H:13]([O:15][C:30]2[CH:29]=[C:28]([N+:33]([O-:35])=[O:34])[CH:27]=[C:26]([F:25])[CH:31]=2)[CH2:12][N:11]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 752721,3-Difluoro-5-nitrobenzeneHCID 11174939HCID 11174939, compound

Product 1

HCID 59751405(2S,4R)-tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)-4-(3-fluoro-5-nitrophenoxy)pyrrolidine-1-carboxylateYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of (2S,4R)-tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)-4-hydroxypyrrolidine-1-carboxylate (1 equiv) in DMF (0.5 M) was added NaH (1.3 equiv) as a solid. After stirring for 30 minutes at 0° C., 3,5-difluoronitrobenzene (1.2 equiv) was added by syringe. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction was quenched by the addition of water, and the mixture was diluted with EtOAc. The organic layer was washed four times with water and once with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification by flash chromatography (10-20% EtOAc/Hexanes) provided the title compound in 66% yield.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred overnight
  3. customThe reaction was quenched by the addition of water
  4. additionthe mixture was diluted with EtOAc
  5. washThe organic layer was washed four times with water
  6. dry with materialonce with brine, dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by flash chromatography (10-20% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-bcf06f7e1f8841cb9057c9ca80a55358
Source dataset
uspto-grants-2009_05
Patent number
US07538223B2

Linked notes

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