Water → ethyl 1-({2-[2-fluoro-3-(trifluoromethyl)phenyl]-5-methyl-1,3-thiazol-4-yl}methyl)-1H-pyrazole-4-carboxylate

HRID 1257387Notes

Reaction equation

HRID 1257387 reaction equation
Br[C:2]1[S:3][C:4]([CH3:18])=[C:5]([CH2:7][N:8]2[CH:12]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:10]=[N:9]2)[N:6]=1.[F:19][C:20]1[C:25]([C:26]([F:29])([F:28])[F:27])=[CH:24][CH:23]=[CH:22][C:21]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.C(O)C>[F:19][C:20]1[C:25]([C:26]([F:27])([F:28])[F:29])=[CH:24][CH:23]=[CH:22][C:21]=1[C:2]1[S:3][C:4]([CH3:18])=[C:5]([CH2:7][N:8]2[CH:12]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:10]=[N:9]2)[N:6]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 162171692-Fluoro-3-(trifluoromethyl)benzeneboronic acidHCID 58127672ethyl 1-[(2-bromo-5-methyl-1,3-thiazol-4-yl)methyl]-1H-pyrazole-4-carboxylate

Product 1

HCID 66939164ethyl 1-({2-[2-fluoro-3-(trifluoromethyl)phenyl]-5-methyl-1,3-thiazol-4-yl}methyl)-1H-pyrazole-4-carboxylateYield 68.1%

Reagents, catalysts & solvents 1

HCID 20074477Dimethoxyethane ethanolSolvent

Conditions

Temperature
90 °C

Procedure

Under a nitrogen atmosphere, to a mixed solution of the compound (230 mg, 0.71 mmol) obtained in Example 80e and 2-fluoro-3-(trifluoromethyl)phenylboronic acid (190 mg, 0.92 mmol) in 1,2-dimethoxyethane/ethanol (v/v=3/1, 4 mL) were added 2N aqueous sodium carbonate solution (0.71 mL, 1.4 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (60 mg, 0.071 mmol), and the mixture was stirred at 90° C. overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The resulting crude title compound was purified by column chromatography (hexane-hexane/ethyl acetate=75/25) to give the title compound (200 mg, 68%) as colorless crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe obtained organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customThe resulting crude title compound was purified by column chromatography (hexane-hexane/ethyl acetate=75/25)

Sources & evidence

ORD record
ord-e6a0412726ea47639db5cbf30286e35a
Source dataset
uspto-grants-2013_06
Patent number
US08461348B2

Reaction notes

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