反应详情

To a 250-mL round-bottomed flask was added (1S,2R,4S)-ethyl 4-hydrazinyl-2-methylcyclohexanecarboxylate hydrochloride (4.00 g, 16.90 mmol) and DIPEA (4.43 ml, 25.3 mmol) in EtOH (84 ml). Then a solution of (Z)-benzyl 2-((dimethylamino)methylene)-4,4,4-trifluoro-3-oxobutanoate (5.09 g, 16.90 mmol) in EtOH (84 ml) was added dropwise into the reaction mixture. The overall reaction mixture was allowed to stir under inert atmosphere, while at ambient temperature overnight. The progress of the reaction was monitored by LC/MS and TLC (30% EtOAc/hexane) which showed mostly desired material LCMS (ESI) m/z 461.2 (M+Na)+, without any starting material remaining. The reaction mixture was concentrated in-vacuo. The crude material was purified by chromatography through an Interchim (25 micron) silica-gel column (200 g), eluting with a gradient of 0-30% EtOAc in hexane, to provide benzyl 1-((1S,3R,4S)-4-(ethoxycarbonyl)-3-methylcyclohexyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (5.631 g, 12.84 mmol, 76% yield) as light-yellow oil. 1H NMR (400 MHz, DMSO-d6) δ 8.14 (s, 1H), 7.32-7.45 (m, 5H), 5.30 (s, 2H), 4.55-4.65 (m, 1H), 4.02-4.15 (m, 2H), 2.65 (td, J=4.50, 11.54 Hz, 1H), 2.13 (dt, J=4.50, 12.42 Hz, 1H), 1.95-2.04 (m, 2H), 1.73 (d, J=4.89 Hz, 3H), 1.16-1.23 (m, 3H), 0.92 (d, J=7.04 Hz, 3H); LCMS (ESI) m/z 461.2 (M+Na)+.

1. concentrationThe reaction mixture was concentrated in-vacuo
2. customThe crude material was purified by chromatography through an Interchim (25 micron) silica-gel column (200 g)
3. washeluting with a gradient of 0-30% EtOAc in hexane