ethyl 1,4,6,7-tetrahydropyrano[4,3-c]pyrazole-3-carboxylate

857177-01-6

518990-21-1

Ethyl 2-oxo-2-(4-oxotetrahydro-2H-pyran-3-yl)acetate (1.1 kg) was used as starting material and dissolved in glacial acetic acid (1.0 kg). The reaction temperature was controlled in the range of 20-30 °C and hydrazine hydrate (910 g, 14.4 mol, 2.9 equiv.) was added slowly dropwise. After the dropwise addition, the reaction was maintained at this temperature and stirred overnight. The progress of the reaction was monitored by thin layer chromatography (TLC) and after confirming the completion of the reaction, water (10 L) and ethyl acetate (5 L) were added to the reaction mixture. The pH was adjusted to 8-9 with solid sodium carbonate and after completion of the adjustment, stirring was continued for 30 min, followed by standing and layering. The aqueous layer was extracted twice with ethyl acetate (5 L × 2). All organic layers were combined and washed with brine (5 L). The organic phase was concentrated under reduced pressure until no significant liquid evaporated, and was pulped by adding petroleum ether (2 L). After filtration, ethyl 1,4,6,7-tetrahydropyrano[4,3-c]pyrazole-3-carboxylate (915 g, UPLC purity: 99%) was obtained as white crude product.