反应详情

To a solution of 2′-chloro-4′,4′-difluoro-4′,5′-dihydrospiro[piperidine-4,7′-thieno[2,3-c]pyran]hydrochloride (0.35 g, 1.1 mmol) and ethyl 1-(3-chloropyridin-2-yl)-4-formyl-pyrazole-3-carboxylate (0.3 g, 1.0 mmol) in 1,2-dichloroethane (20 mL) is added N-methyl morpholine (0.33 g, 3.2 mmol) and molecular sieves (0.10 g). The reaction mixture is stirred at room temperature for 1 h. Sodium triacetoxyborohydride (0.58 g, 2.7 mmol) is added and stirred at room temperature for 16 h. After completion, the reaction mixture is filtered through celite and partitioned between dichloromethane (15 mL) and water (15 mL). The aqueous phase is extracted with dichloromethane (3×30 mL) and the combined organic extracts are dried over sodium sulfate and concentrated in vacuo. The crude mixture is purified by column chromatography over silica gel eluting with dichloromethane/methanol (98:2) to yield 0.4 g (67%) of ethyl 4-((2′-chloro-4′,4′-difluoro-4′,5′-dihydrospiro[piperidine-4,7′-thieno[2,3-c]pyran]-1-yl)methyl)-1-(3-chloro-2-pyridyl)-1H-pyrazole-3-carboxylate. MS (m/z): 543 (M+1).

1. stirringstirred at room temperature for 16 h
2. filtrationAfter completion, the reaction mixture is filtered through celite
3. custompartitioned between dichloromethane (15 mL) and water (15 mL)
4. extractionThe aqueous phase is extracted with dichloromethane (3×30 mL)
5. dry with materialthe combined organic extracts are dried over sodium sulfate
6. concentrationconcentrated in vacuo
7. customThe crude mixture is purified by column chromatography over silica gel eluting with dichloromethane/methanol (98:2)