Sulfuric Acid → Z-Pyr-OtBu

HRID 710941Notes

Reaction equation

HRID 710941 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+]>C(Cl)Cl>[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

(S)-1-(Benzyloxycarbonyl)-5-oxopyrrolidine-2-carboxylic acid (100 g) was dissolved in dehydrated methylene chloride (2 L), and under ice cooling, concentrated sulfuric acid (10 mL) and isobutene (213 g) 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, then 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-2262c808b3d248028f5299a2401c276f
Source dataset
uspto-grants-2015_11
Patent number
US09181250B2

Reaction notes

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