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

HRID 642287

Reaction equation

HRID 642287 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[N:8][C:7]=1[CH2:21]Br)=[O:5])[CH3:2].[CH2:23]([O:25][C:26](=[O:36])[CH2:27][NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH3:24].[H-].[Na+]>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[N:8][C:7]=1[CH2:21][N:28]([C:29]([O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[O:30])[CH2:27][C:26]([O:25][CH2:23][CH3:24])=[O:36])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 357729Ethyl 2-((tert-butoxycarbonyl)amino)acetateHCID 179517684-Bromomethyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic Acid Ethyl Ester

Product 1

HCID 684274034-[(tert-Butoxycarbonyl-ethoxycarbonylmethyl-amino)-methyl]-2-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid ethyl esterYield 23.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 4-bromomethyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid ethyl ester (1.05 g, 2.67 mmol), tert-butoxycarbonylamino-acetic acid ethyl ester (540 mg, 2.66 mmol) and sodium hydride (60% in mineral oil, 128 mg, 3.2 mmol) in anhydrous dimethylformamide (10 mL) was stirred at 0° C. for two hours and room temperature for half an hour before it was quenched with brine. The mixture was filtered and the filtrate was extracted with ethyl acetate. 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 (319 mg): MS: (+) m/z 538.9 (M+Na+).

Workup

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

Sources & evidence

ORD record
ord-21d69a1fcdb84e4cb15db075e3f583f3
Source dataset
uspto-grants-2010_04
Patent number
US07696223B2

Linked notes

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