Imidazole → ethyl 2-{[(2R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-oxo-1-pyrrolidinyl]methyl}-1,3-thiazole-4-carboxylate

HRID 1888324Notes

Reaction equation

HRID 1888324 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]1[CH2:14][CH2:13][C:12](=[O:15])[N:11]1[CH2:16][C:17](=[S:19])[NH2:18])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Br[CH2:21][C:22](=O)[C:23]([O:25][CH2:26][CH3:27])=[O:24].N1C=CN=C1.[Si](Cl)(C(C)(C)C)(C)C>CN(C)C=O.O.C(OCC)(=O)C>[Si:1]([O:8][CH2:9][C@H:10]1[CH2:14][CH2:13][C:12](=[O:15])[N:11]1[CH2:16][C:17]1[S:19][CH:21]=[C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[N:18]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 66144Ethyl bromopyruvateHCID 866500602-[(2R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-oxo-1-pyrrolidinyl]ethanethioamide

Product 1

HCID 66857942ethyl 2-{[(2R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-oxo-1-pyrrolidinyl]methyl}-1,3-thiazole-4-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the compound 68 (4.50 g) in dimethylformamide (15.0 mL) was ethyl bromopyruvate (2.33 mL) at 0° C. and the solution was stirred at room temperature for 2 Hours. To the reaction solution were added imidazole (4.08 g) and tert-butyldimethylsilyl chloride (4.52 g) at 0° C. and the solution was stirred at room temperature for 2 Hours. To the reaction solution were added ethyl acetate and water and then the solution was separated. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with an aqueous saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate and concentrated. The obtained residue was purified by column chromatography on silica gel (n-hexane:ethyl acetate=3:2→2:3) to give the title compound (4.75 g) having the following physical data.

Workup

  1. customat 0° C.
  2. stirringthe solution was stirred at room temperature for 2 Hours
  3. customthe solution was separated
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washThe combined organic layer was washed with an aqueous saturated sodium bicarbonate solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe obtained residue was purified by column chromatography on silica gel (n-hexane:ethyl acetate=3:2→2:3)

Sources & evidence

ORD record
ord-f0e08713e95f49609e504eddfe8c31a2
Source dataset
uspto-grants-2013_08
Patent number
US08501793B2

Reaction notes

Loading…