Sodium hydride → 4-[(tert-Butoxycarbonyl-ethoxycarbonylmethyl-amino)-methyl]-2-(methyl-phenyl-amino)-thiazole-5-carboxylic acid ethyl ester

HRID 642309Notes

Reaction equation

HRID 642309 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([N:11]([CH3:18])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:8][C:7]=1[CH2:19]Br)=[O:5])[CH3:2].[CH2:21]([O:23][C:24](=[O:34])[CH2:25][NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH3:22].[H-].[Na+]>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([N:11]([CH3:18])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:8][C:7]=1[CH2:19][N:26]([C:27]([O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:28])[CH2:25][C:24]([O:23][CH2:21][CH3:22])=[O:34])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 357729Ethyl 2-((tert-butoxycarbonyl)amino)acetateHCID 684285544-Bromomethyl-2-(methyl-phenyl-amino)-thiazole-5-carboxylic acid ethyl ester

Product 1

HCID 684283884-[(tert-Butoxycarbonyl-ethoxycarbonylmethyl-amino)-methyl]-2-(methyl-phenyl-amino)-thiazole-5-carboxylic acid ethyl esterYield 49.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 4-bromomethyl-2-(methyl-phenyl-amino)-thiazole-5-carboxylic acid ethyl ester (974 mg, 2.75 mmol), tert-butoxycarbonylamino-acetic acid ethyl ester (559 mg, 2.75 mmol) and sodium hydride (60% in mineral oil, 132 mg, 3.30 mmol) in anhydrous dimethylformamide (10 mL) was stirred at 0° C. for two hours and room temperature for 18 h before it was quenched with brine. It was partitioned between ethyl acetate and water. The organic layer was washed with water, brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel with a gradient of ethyl acetate and hexanes to give the title compound as a yellow oil (652 mg): MS: (+) m/z 500.0 (M+Na+).

Workup

  1. customwas quenched with brine
  2. customIt was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with water, brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel with a gradient of ethyl acetate and hexanes

Sources & evidence

ORD record
ord-9baf9fc101b3485894e201eef53d28b1
Source dataset
uspto-grants-2010_04
Patent number
US07696223B2

Reaction notes

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