Water → (2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

HRID 1029643Notes

Reaction equation

HRID 1029643 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]([OH:16])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:17](=O)([O-])[O-].[K+].[K+].CI.O>CN(C)C=O.C(OCC)(=O)C>[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])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid

Product 1

HCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterYield 96.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2S,4R)-1-(tert-butoxycarbonyl)-2-carboxy-4-hydroxypyrrolidine (103 g) and potassium carbonate (64.6 g) in dimethylformamide (500 ml) was added methyl iodide (33.2 ml) at 0° C., and the mixture was stirred for three hours. The reaction mixture was poured into a mixture of water (1 l) and ethyl acetate (1 l), and the organic layer was separated, washed in turn with water (500 ml) and brine, and dried over magnesium sulfate. Evaporation of the solvent gave an oil, which was chromatographed on silica gel (800 ml) eluting with a mixture of hexane and ethyl acetate (1:2, V/V) to give (2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxy-2-methoxycarbonylpyrrolidine (105.2 g).

Workup

  1. customthe organic layer was separated
  2. washwashed in turn with water (500 ml) and brine
  3. dry with materialdried over magnesium sulfate
  4. customEvaporation of the solvent
  5. customgave an oil, which
  6. customwas chromatographed on silica gel (800 ml)
  7. washeluting with a mixture of hexane and ethyl acetate (1:2, V/V)

Sources & evidence

ORD record
ord-0c82632f7a694962a408f9a78b0e1eb2
Source dataset
uspto-grants-1992_04
Patent number
US05102877

Reaction notes

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