Sodium hydride → {4-[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-indol-1-yl}-acetic acid tert-butyl ester

HRID 1767870Notes

Reaction equation

HRID 1767870 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=2)[S:5][C:6]=1[CH2:7][O:8][C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[CH:12][NH:13]2.[C:28]([O:32][C:33](=[O:36])[CH2:34]Br)([CH3:31])([CH3:30])[CH3:29].[H-].[Na+]>CN(C=O)C>[C:28]([O:32][C:33](=[O:36])[CH2:34][N:13]1[C:14]2[C:10](=[C:9]([O:8][CH2:7][C:6]3[S:5][C:4]([C:18]4[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:25])[F:26])=[CH:20][CH:19]=4)=[N:3][C:2]=3[CH3:1])[CH:17]=[CH:16][CH:15]=2)[CH:11]=[CH:12]1)([CH3:31])([CH3:30])[CH3:29]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 115746051H-Indole, 4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-5-thiazolyl]methoxy]-

Product 1

HCID 11699008{4-[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-indol-1-yl}-acetic acid tert-butyl esterYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-1H-indole (50 mg, 130 μmol) and bromo-acetic acid tert-butyl ester (20 μl, 140 μmol) in DMF (4 ml) was added sodium hydride (55%, 8 mg, 176 μmol) under an argon atmosphere at 0° C. The mixture was naturally warmed to room temperature, stirred for 72 h, poured onto 1 N HCl/ice water 1/1 and extracted three times with dichloromethane. The combined organic layers were washed with water and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography (silica gel, heptane/AcOEt) to give 50 mg (99 μmol, 77%) of the title compound as light yellow oil.

Workup

  1. extractionextracted three times with dichloromethane
  2. washThe combined organic layers were washed with water
  3. dry with materialdried over sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. customthe residue purified by column chromatography (silica gel, heptane/AcOEt)

Sources & evidence

ORD record
ord-866a3b1e73d145f0bf3b39e78bd544de
Source dataset
uspto-grants-2007_06
Patent number
US07235572B2

Reaction notes

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