Hydrochloric Acid → (1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl(8-chloro-6-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methanone
Reaction equation
Cl.[C@H:2]12[CH2:8][C@H:5]([NH:6][CH2:7]1)[CH2:4][O:3]2.C1(C)C=CC=CC=1.C[Al](C)C.[Cl:20][C:21]1[C:22]2[N:23]([C:31]([C:34](OCC)=[O:35])=[N:32][N:33]=2)[CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1.Cl>C1COCC1>[C@H:2]12[CH2:8][C@H:5]([N:6]([C:34]([C:31]3[N:23]4[CH:24]=[C:25]([C:27]([F:29])([F:28])[F:30])[CH:26]=[C:21]([Cl:20])[C:22]4=[N:33][N:32]=3)=[O:35])[CH2:7]1)[CH2:4][O:3]2Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a mixture of (1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane hydrochloride (100 mg) and anhydrous THF (4 mL) was added dropwise trimethylaluminium toluene solution (1.8 M, 0.410 mL) in an ice bath. The reaction solution was stirred at the same temperature for 1 hr under argon gas atmosphere, ethyl 8-chloro-6-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-3-carboxylate (180 mg) was added thereto, and the mixture was stirred at room temperature for 2 days. The reaction mixture was slowly added to 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (47 mg).
Workup
- stirringthe mixture was stirred at room temperature for 2 days
- extractionthe mixture was extracted with ethyl acetate
- dry with materialThe organic layer was dried over anhydrous magnesium sulfate
- customthe solvent was evaporated under reduced pressure
- customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
Sources & evidence
- ORD record
- ord-1a99a00d56a84ca486ff245341ebe8ee
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09296746B2
Reaction notes
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