Acetone → 1-tert-butyl 2-methyl (2S)-4-oxopyrrolidine-1,2-dicarboxylate

HRID 557920Notes

Reaction equation

HRID 557920 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([OH:13])[CH2:10][C@H:9]1[C:14]([O:16][CH3:17])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)=O.O.S(=O)(=O)(O)O>CCOCC.[O-2].[Cr+6].[O-2].[O-2].C(O)(C)C>[O:13]=[C:11]1[CH2:12][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C@H:9]([C:14]([O:16][CH3:17])=[O:15])[CH2:10]1

Participants

8

Reactant 4

HCID 180AcetoneHCID 962WaterHCID 1118Sulfuric AcidHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Product 1

HCID 109884851-tert-butyl 2-methyl (2S)-4-oxopyrrolidine-1,2-dicarboxylateYield 56.5%

Reagents, catalysts & solvents 3

HCID 10219390chromium (VI) trioxideCatalystHCID 3283Diethyl EtherSolventHCID 3776IsopropanolSolvent

Procedure

Methyl (2S,4R)—N-tert-butoxycarbonyl-4-hydroxy-2-pyrrolidinecarboxylate (2.00 g, 0.00815 mol) was dissolved in acetone (50.0 mL, 0.681 mol) and ether (50 mL). To the solution with stirring, was added a solution of chromium(VI) oxide (1.90 g, 0.0190 mol) in water (5.50 mL, 0.305 mol) and sulfuric acid (1.60 mL, 0.0294 mol) over 15 minutes with the presence of an ice-water bath to maintain the reaction temperature at about room temperature. The mixture was stirred at rt for 10 minutes and then iso-propanol (10 mL) was added. The mixture was stirred for an additional 5 min. The mixture was filtered through a pad of silica gel plus potassium carbonate. The filtrated was concentrated and the residue was purified by Combiflash with ethyl acetate/hexane (25%) to give the desired product (1.12 g).

Workup

  1. temperatureto maintain the reaction temperature at about room temperature
  2. stirringThe mixture was stirred at rt for 10 minutes
  3. stirringThe mixture was stirred for an additional 5 min
  4. filtrationThe mixture was filtered through a pad of silica gel plus potassium carbonate
  5. concentrationThe filtrated was concentrated
  6. customthe residue was purified by Combiflash with ethyl acetate/hexane (25%)

Sources & evidence

ORD record
ord-75e872af806f4538bd831c69eb9edd65
Source dataset
uspto-grants-2011_11
Patent number
US08058288B2

Reaction notes

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