Methyl Acetate → (2S,4R)-N-tert-Butoxycarbonyl-4-tert-butyldimethylsiloxy-2-[1-hydroxy-2-(methoxycarbonyl)ethyl]pyrrolidine

HRID 1078721Notes

Reaction equation

HRID 1078721 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Na+].[C:11]([O:14][CH3:15])(=[O:13])[CH3:12].[C:16]([O:20][C:21]([N:23]1[CH2:29][C@H:28]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[CH2:27][C@H:24]1[CH:25]=[O:26])=[O:22])([CH3:19])([CH3:18])[CH3:17].[Cl-].[NH4+]>O1CCCC1>[C:16]([O:20][C:21]([N:23]1[CH2:29][C@H:28]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[CH2:27][C@H:24]1[CH:25]([OH:26])[CH2:12][C:11]([O:14][CH3:15])=[O:13])=[O:22])([CH3:19])([CH3:18])[CH3:17]

Participants

6

Reactant 4

HCID 6584Methyl AcetateHCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 10969557tert-Butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylate

Product 1

HCID 57107882(2S,4R)-N-tert-Butoxycarbonyl-4-tert-butyldimethylsiloxy-2-[1-hydroxy-2-(methoxycarbonyl)ethyl]pyrrolidineYield 94.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To tetrahydrofuran (5 ml) were successively dropwise added a 1.0M sodium hexamethyldisilazide--tetrahydrofuran solution (0.910 ml, 0.910 mmol) and methyl acetate (72.0 μl) at -78° C. The mixture was stirred for 30 minutes, and a tetrahydrofuran solution of (2S,4R)-N-tert-butoxycarbonyl-4-tert-butyldimethylsiloxyprolinal (200 mg, 0.607 mmol) was added thereto at the same temperature. This solution was stirred for 30 minutes. Saturated aqueous ammonium chloride was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo. The residue was purified by silica gel column chromatography (heptane-ethyl acetate=3:1) to give the title compound [232 mg, yield: 94.7%; (R)-isomer (polar compound):(S)-isomer (less polar compound)=6.27:1].

Workup

  1. customat -78° C
  2. stirringThis solution was stirred for 30 minutes
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was removed in vacuo
  7. customThe residue was purified by silica gel column chromatography (heptane-ethyl acetate=3:1)

Sources & evidence

ORD record
ord-cfc2a7c19b864fce8883959ad68c5f3e
Source dataset
uspto-grants-1996_08
Patent number
US05550121

Reaction notes

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