Hydrochloric Acid → 2-(4-Difluoromethyl-phenyl)-2,2-difluoro-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethanol

HRID 1172667Notes

Reaction equation

HRID 1172667 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=2)[S:5][C:6]=1[CH:7]=[O:8].Br[C:20]([F:31])([F:30])[C:21]1[CH:26]=[CH:25][C:24]([CH:27]([F:29])[F:28])=[CH:23][CH:22]=1.[In].Cl>CN(C)C=O>[F:28][CH:27]([F:29])[C:24]1[CH:23]=[CH:22][C:21]([C:20]([F:31])([F:30])[CH:7]([C:6]2[S:5][C:4]([C:9]3[CH:10]=[CH:11][C:12]([C:15]([F:18])([F:16])[F:17])=[CH:13][CH:14]=3)=[N:3][C:2]=2[CH3:1])[OH:8])=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 27788231-(Bromodifluoromethyl)-4-(difluoromethyl)benzene2×HCID 27828994-Methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carbaldehydeHCID 5359967Indium

Product 1

HCID 595563802-(4-Difluoromethyl-phenyl)-2,2-difluoro-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethanolYield 37.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1.0 g 4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbaldehyde and 1.42 g 4-(bromodifluoromethyl)-1-(difluoromethyl)benzene in 10 ml dimethylformamide 508 mg Indium were added and the resulting suspension was stirred in an ultrasonic bath for twelve hours. Then additional 1.42 g 4-(bromodifluoromethyl)-1-(difluoromethyl)benzene and 508 mg Indium were added and the resulting suspension was stirred in an ultrasonic bath for additional twelve hours. Then 20 ml 1 N hydrochloric acid were added and the mixture stirred at room temperature for thirty minutes. The mixture was extracted three times with portions of 50 ml ethyl acetate. The combined organic layers were dried over MgSO4. The solvent was evaporated in vacuo. The resulting residue was purified by reversed phase HPLC to obtain 620 mg 2-(4-Difluoromethyl-phenyl)-2,2-difluoro-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethanol as a colorless lyophilisate.

Workup

  1. stirringthe resulting suspension was stirred in an ultrasonic bath for additional twelve hours
  2. stirringthe mixture stirred at room temperature for thirty minutes
  3. extractionThe mixture was extracted three times with portions of 50 ml ethyl acetate
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. customThe solvent was evaporated in vacuo
  6. customThe resulting residue was purified by reversed phase HPLC

Sources & evidence

ORD record
ord-5e40d565316945fbbee7f95c63c46b54
Source dataset
uspto-grants-2010_11
Patent number
US07834030B2

Reaction notes

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