反应详情

To tert-butyl 3-(diethoxymethyl)-6-fluoro-4-oxo-spiro[chromane-2,4′-piperidine]-1′-carboxylate (3.81 g, 8.71 mmol) was added hydrochloric acid (32.7 mL of 4.0 M in dioxane, 130 mmol). The reaction mixture was allowed to stir at room temperature for 2 hours. The solvent was removed under vacuum, and the obtained solid was azeotroped with EtOH (1×30 mL). The resulting solid was suspended in EtOH (30.5 mL) and was treated with methylhydrazine (556 μL, 10.5 mmol) at 40° C. for 4 h. The mixture was then heated at 80° C. for 1 h resulting in a yellow solution with an off white precipitate. The solid was collected to give 8-fluoro-2-methyl-2H-spiro[chromeno[4,3-c]pyrazole-4,4′-piperidine]hydrochloride (798 mg, 26%). ESI-MS m/z calc. 273.1. found 274.5 (M+1)+. Retention time 0.83 minutes (3 min run). Note: The yellow mother liquor was evaporated to give a mixture of methyl regioisomers (1.71 g).

1. customThe solvent was removed under vacuum
2. customthe obtained solid was azeotroped with EtOH (1×30 mL)
3. temperatureThe mixture was then heated at 80° C. for 1 h
4. customresulting in a yellow solution with an off white precipitate
5. customThe solid was collected