Hydrochloric Acid → 2,2,2-Trifluoro-1-{3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-8-(3,4,5-trifluorophenoxy)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-8-yl}ethanol

HRID 71189Notes

Reaction equation

HRID 71189 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:15]2[N:19]3[CH2:20][CH2:21][CH2:22][C:23]([O:26][C:27]4[CH:32]=[C:31]([F:33])[C:30]([F:34])=[C:29]([F:35])[CH:28]=4)([CH:24]=[O:25])[C:18]3=[N:17][N:16]=2)[CH:6]=[CH:7][C:8]=1[C:9]1[O:13][C:12]([CH3:14])=[N:11][CH:10]=1.[F:36][C:37]([Si](C)(C)C)([F:39])[F:38].CCCC[N+](CCCC)(CCCC)CCCC.[F-].Cl>C1COCC1.C(=O)([O-])O.[Na+]>[F:36][C:37]([F:39])([F:38])[CH:24]([C:23]1([O:26][C:27]2[CH:28]=[C:29]([F:35])[C:30]([F:34])=[C:31]([F:33])[CH:32]=2)[CH2:22][CH2:21][CH2:20][N:19]2[C:15]([C:5]3[CH:6]=[CH:7][C:8]([C:9]4[O:13][C:12]([CH3:14])=[N:11][CH:10]=4)=[C:3]([O:2][CH3:1])[CH:4]=3)=[N:16][N:17]=[C:18]12)[OH:25]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 866629793-[3-Methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-8-(3,4,5-trifluorophenoxy)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carbaldehyde

Product 1

HCID 866629782,2,2-Trifluoro-1-{3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-8-(3,4,5-trifluorophenoxy)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-8-yl}ethanol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a mixture of 3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-8-(3,4,5-trifluorophenoxy)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carbaldehyde (150 mg) and (trifluoromethyl)trimethylsilane (0.137 mL) in THF (1.5 mL) was added TBAF (1M THF solution, 0.062 mL) under an argon atmosphere at room temperature. The reaction mixture was stirred at room temperature for 2 hr, 1N hydrochloric acid (3 mL) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was separated, washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane), and further recrystallized from ethyl acetate/hexane to give the title compound (38.8 mg).

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. extractionthe mixture was extracted with ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane)
  8. customfurther recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-dac2057427e24fdc91cc3b308d6d2d51
Source dataset
uspto-grants-2014_09
Patent number
US08822699B2

Reaction notes

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