Benzyl chloroformate → Z-Pyr-OtBu

HRID 481243Notes

Reaction equation

HRID 481243 reaction equation
[O:1]=[C:2]1[NH:6][C@H:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4][CH2:3]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH:24]1[CH:29]=[CH:28][C:27]([CH2:30][O:31][C:32](Cl)=[O:33])=[CH:26][CH:25]=1>C1COCC1>[O:1]=[C:2]1[N:6]([C:32]([O:31][CH2:30][C:27]2[CH:28]=[CH:29][CH:24]=[CH:25][CH:26]=2)=[O:33])[C@H:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 2733832Lithium HexamethyldisilazideHCID 10888648tert-Butyl 5-oxo-L-prolinate

Product 1

HCID 10615573Z-Pyr-OtBuYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 1a (2.00 g, 10.8 mmol) in 50 mL THF at −78° C., was added LiHMDS (1M THF, 11.9 mL, 11.9 mmol). The mixture was stirred at −78° C. for 20 min, then Cbz-Cl was added, dropwise over 5 min. The mixture was stirred at −78° for 20 min, then quenched with sat. NH4Cl. The mixture was diluted with H2O and extracted with EtOAc (3×). The organic phase was washed with brine, dried (Na2SO4), and concentrated. The crude product was purified by flash chromatography (30 to 35 to 40% EtOAc/hexanes) to afford 3.12 g (90%) of 8a as a colorless solid.

Workup

  1. stirringThe mixture was stirred at −78° for 20 min
  2. customquenched with sat. NH4Cl
  3. additionThe mixture was diluted with H2O
  4. extractionextracted with EtOAc (3×)
  5. washThe organic phase was washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (30 to 35 to 40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-10dd75fc3b8b47ee92548b1796aa225a
Source dataset
uspto-grants-2003_11
Patent number
US06653295B2

Reaction notes

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