Imidazole → (2S,4R)-1-tert-Butyl 2-methyl 4-((tert-butyldimethylsilyl)oxy)pyrrolidine-1,2-dicarboxylate

HRID 620789Notes

Reaction equation

HRID 620789 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].[Si:18](Cl)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19].N1C=CN=C1.O>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[CH2:10][C@H:9]1[C:14]([O:16][CH3:17])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 28928tert-Butyldimethylsilyl chlorideHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Product 1

HCID 10618477(2S,4R)-1-tert-Butyl 2-methyl 4-((tert-butyldimethylsilyl)oxy)pyrrolidine-1,2-dicarboxylateYield 95.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2S,4R)-1-t-butoxycarbonyl-4-hydroxy-2-methoxycarbonylpyrrolidine (20.0 g) and t-butyldimethylsilyl chloride (18.44 g) in dimethylformamide (60 ml) was added imidazole (11.1 g) under ice-cooling, and the mixture was stirred at 0°-10° C. for 1 hour and then at ambient temperature for 18 hours. The reaction mixture was poured into water (300 ml) and extracted with ethyl acetate (100 ml×3). The combined organic layer was washed with water (200 ml×2) and brine (150 ml) successively, dried over magnesium sulfate, and concentrated under reduced pressure to give a syrup. The syrup was subjected to a column chromatography on silica gel (250 g) to give (2S,4R)-1-t-butoxycarbonyl-4-t-butyldimethylsilyloxy-2-methoxycarbonylpyrrolidine (27.95 g).

Workup

  1. temperaturecooling
  2. waitat ambient temperature for 18 hours
  3. extractionextracted with ethyl acetate (100 ml×3)
  4. washThe combined organic layer was washed with water (200 ml×2) and brine (150 ml) successively
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give a syrup

Sources & evidence

ORD record
ord-ad2a43c35ede497a95d2370222ff0fb1
Source dataset
uspto-grants-1989_04
Patent number
US04822787

Reaction notes

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