Benzyl chloroformate → (S)-benzyl 2-((tert-butyldimethylsilyloxy)methyl)-5-oxopyrrolidine-1-carboxylate

HRID 416359Notes

Reaction equation

HRID 416359 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]1[NH:14][C:13](=[O:15])[CH2:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CC([O-])(C)C.[K+].[CH:22]1[CH:27]=[CH:26][C:25]([CH2:28][O:29][C:30](Cl)=[O:31])=[CH:24][CH:23]=1>C1COCC1>[Si:1]([O:8][CH2:9][C@@H:10]1[CH2:11][CH2:12][C:13](=[O:15])[N:14]1[C:30]([O:29][CH2:28][C:25]1[CH:26]=[CH:27][CH:22]=[CH:23][CH:24]=1)=[O:31])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 10263224(S)-5-(((tert-Butyldimethylsilyl)oxy)methyl)pyrrolidin-2-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 12078685(S)-benzyl 2-((tert-butyldimethylsilyloxy)methyl)-5-oxopyrrolidine-1-carboxylateYield 91.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-5-((tert-butyldimethylsilyloxy)methyl)pyrrolidin-2-one (48.5 g, 0.21 mol) in THF (100 mL) was added t-BuOK (30.8 g, 0.27 mol) at 0° C. The mixture was stirred at 0° C. for 30 min followed by addition of Cbz-Cl (40.4 mL, 0.27 mol) dropwise at 0° C. The resulting mixture was stirred at RT overnight, quenched with saturated NH4Cl, concentrated to a small amount, and diluted with EtOAc. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel column using a mixture of EtOAc and hexanes to give (S)-benzyl 2-((tert-butyldimethylsilyloxy)methyl)-5-oxopyrrolidine-1-carboxylate (70 g, 91%). LRMS (M+H-44) m/z 320.2.

Workup

  1. stirringThe resulting mixture was stirred at RT overnight
  2. customquenched with saturated NH4Cl
  3. concentrationconcentrated to a small amount
  4. additiondiluted with EtOAc
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified on silica gel column
  10. additiona mixture of EtOAc and hexanes

Sources & evidence

ORD record
ord-a82069e2b78f4fb78d3bb50435be918c
Source dataset
uspto-grants-2012_01
Patent number
US08088793B2

Reaction notes

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