Imidazole → (2S,3R)-3-(tert-Butyldimethylsilanyloxy)-2-methylpyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester-2-methyl ester

HRID 501604Notes

Reaction equation

HRID 501604 reaction equation
[CH3:1][O:2][C:3]([C@:5]1([CH3:18])[C@H:9]([OH:10])[CH2:8][CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4].N1C=CN=C1.[Si:24](Cl)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25]>C(Cl)Cl>[CH3:1][O:2][C:3]([C@:5]1([CH3:18])[C@H:9]([O:10][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:8][CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 59754263(2S,3R)-3-Hydroxy-2-methylpyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Product 1

HCID 68459339(2S,3R)-3-(tert-Butyldimethylsilanyloxy)-2-methylpyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester-2-methyl esterYield 87.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2S,3R)-3-Hydroxy-2-methylpyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester-2-methyl ester (25A) (362 mg, 1.39 mmol) in CH2Cl2 (4 mL) was added imidazole (284 mg, 4.17 mmol) then tert-butydimethylsilyl chloride (1.05 g, 6.95 mmol). After stirring overnight, the reaction was partitioned between H2O and CH2Cl2. The CH2Cl2 layer was washed with 1M H3PO4 (2×) and brine, dried (MgSO4), then filtered and concentrated under reduced pressure. The residue was chromatographed (silica gel) eluting with 30% EtOAc/hexane to yield the title compound (456 mg) as a white solid.

Workup

  1. customthe reaction was partitioned between H2O and CH2Cl2
  2. washThe CH2Cl2 layer was washed with 1M H3PO4 (2×) and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was chromatographed (silica gel)
  7. washeluting with 30% EtOAc/hexane

Sources & evidence

ORD record
ord-5a2e3c1da3ca42f3a8599925618fd5c3
Source dataset
uspto-grants-2010_08
Patent number
US07772267B2

Reaction notes

Loading…