Sulfuric Acid → Z-Pyr-OtBu

HRID 575866Notes

Reaction equation

HRID 575866 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[C:15](=[O:16])[CH2:14][CH2:13][C@H:12]1[C:17]([OH:19])=[O:18])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[CH2:25]=[C:26]([CH3:28])[CH3:27].C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[O:16]=[C:15]1[N:11]([C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[C@H:12]([C:17]([O:19][C:26]([CH3:28])([CH3:27])[CH3:25])=[O:18])[CH2:13][CH2:14]1

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 8255IsobutyleneHCID 10340Sodium CarbonateHCID 6376481-(Phenylmethyl) (2S)-5-oxo-1,2-pyrrolidinedicarboxylate

Product 1

HCID 10615573Z-Pyr-OtBuYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

100 g of (S)-1-(benzyloxycarbonyl)-5-oxopyrrolidine-2-carboxylic acid was dissolved in dehydrated dichloromethane (2 L), and under ice cooling, concentrated sulfuric acid (10 mL) and 213 g of isobutene were added, followed by stirring overnight at +20° C. or less. The reaction mixture was added to cold aqueous sodium carbonate solution while paying attention to effervescence, followed by liquid separation of the organic phase, washing with saturated brine and drying over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (hexane/ethyl acetate=7/3), and crystallized with hexane/ethyl acetate to afford 80 g of the title compound as a colorless crystalline powder (yield 67%). Enantiomeric excess: 99.9% ee or more (CHIRALPAK AD-H, 4.6×150 mm, UV 210 nm, hexane/ethanol=2/1, flow rate 1 mL/min., retention time 4.2 min.).

Workup

  1. customfollowed by liquid separation of the organic phase
  2. washwashing with saturated brine
  3. dry with materialdrying over anhydrous magnesium sulfate
  4. concentrationthe solvent was concentrated under reduced pressure
  5. customcrystallized with hexane/ethyl acetate

Sources & evidence

ORD record
ord-704d73fbb26949f9a70a2e582a79884f
Source dataset
uspto-grants-2015_05
Patent number
US09035062B2

Reaction notes

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