Citric Acid → (S)-4-(1-hydroxy-1-methyl-ethyl)-5-oxo-pyrrolidine-1,2-dicarboxylic acid 2-benzylester 1-tert-butyl ester

HRID 1099321Notes

Reaction equation

HRID 1099321 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[C:11]([O:15][C:16]([N:18]1[C:22](=[O:23])[CH2:21][CH2:20][C@H:19]1[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25])=[O:17])([CH3:14])([CH3:13])[CH3:12].B(F)(F)F.CCOCC.C(O)(=O)[CH2:44][C:45](CC(O)=O)([C:47](O)=O)[OH:46]>O1CCCC1.CC(C)=O>[C:11]([O:15][C:16]([N:18]1[C:22](=[O:23])[CH:21]([C:45]([OH:46])([CH3:47])[CH3:44])[CH2:20][C@H:19]1[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25])=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 8000Boron trifluoride etherateHCID 2733832Lithium HexamethyldisilazideHCID 80274822-Benzyl 1-tert-butyl (2S)-5-oxopyrrolidine-1,2-dicarboxylate

Product 1

HCID 58298416(S)-4-(1-hydroxy-1-methyl-ethyl)-5-oxo-pyrrolidine-1,2-dicarboxylic acid 2-benzylester 1-tert-butyl ester

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of lithium hexamethyldisilazide in tetrahydrofuran is cooled to −78° C. and treated with a solution of 15.95 g of (S)-5-oxo-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester in 100 mL of tetrahydrofuran maintaining the temperature at −78° C. The resulting mixture was stirred for 40 minutes and a mixture of 40 mL of acetone and 7 mL of boron trifluoride diethyl etherate added within 20 minutes. The reaction mixture is stirred for 2.5 hours at −78° C. and 300 mL of a 10% solution of citric acid added and the reaction mixture warmed to room temperature. The layers are separated and the aqueous layer is re-extracted with 300 mL of dichloromethane. The combined organic layers are dried, filtered and the solvent removed to give (S)-4-(1-hydroxy-1-methyl-ethyl)-5-oxo-pyrrolidine-1,2-dicarboxylic acid 2-benzylester 1-tert-butyl ester as an oil.

Workup

  1. additionadded within 20 minutes
  2. stirringThe reaction mixture is stirred for 2.5 hours at −78° C.
  3. customThe layers are separated
  4. extractionthe aqueous layer is re-extracted with 300 mL of dichloromethane
  5. customThe combined organic layers are dried
  6. filtrationfiltered
  7. customthe solvent removed

Sources & evidence

ORD record
ord-ac6358852e1e4535b3fdb75f094b43cf
Source dataset
uspto-grants-2012_03
Patent number
US08143416B2

Reaction notes

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