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

HRID 1078722Notes

Reaction equation

HRID 1078722 reaction equation
C(N(CC)CCN(CC)CC)C.C[Si](C)(C)[N-][Si](C)(C)C.[Na+].[C:23]([O:26][CH3:27])(=[O:25])[CH3:24].[C:28]([O:32][C:33]([N:35]1[CH2:41][C@H:40]([O:42][Si:43]([C:46]([CH3:49])([CH3:48])[CH3:47])([CH3:45])[CH3:44])[CH2:39][C@H:36]1[CH:37]=[O:38])=[O:34])([CH3:31])([CH3:30])[CH3:29].[Cl-].[NH4+]>O1CCCC1>[C:28]([O:32][C:33]([N:35]1[CH2:41][C@H:40]([O:42][Si:43]([C:46]([CH3:49])([CH3:48])[CH3:47])([CH3:45])[CH3:44])[CH2:39][C@H:36]1[CH:37]([OH:38])[CH2:24][C:23]([O:26][CH3:27])=[O:25])=[O:34])([CH3:31])([CH3:30])[CH3:29]

Participants

7

Reactant 5

HCID 6584Methyl AcetateHCID 25517Ammonium ChlorideHCID 67423N,N,N',N'-Tetraethylethylenediamine List AcronymsHCID 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 87.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a mixture of tetrahydrofuran (45 ml) and tetraethylethylenediamine (1.5 ml) were successively added a 1.0M sodium hexamethyldisilazide--tetrahydrofuran solution (0.892 ml) and methyl acetate (71.2 μl) at -78° C. The mixture was stirred for 30 minutes, and then a tetrahydrofuran solution of (2S,4R)-N-tert-butoxycarbonyl-4-(tert-butyldimethylsiloxy)prolinal (196 mg) was added thereto. This solution was stirred for 30 minutes. Saturated aqueous ammonium chloride was added to the reaction solution. 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 obtain the title compound [209 mg, yield: 87.1%; (R)-isomer (polar compound):(S)-isomer (less polar compound)=1.82:1].

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-1da1f5a7568c451280c191a38c8cb6a9
Source dataset
uspto-grants-1996_08
Patent number
US05550121

Reaction notes

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