p-Toluenesulfonic acid → [1-Acetyl-3-(2,5-difluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-5-yl]methanol

Participants

Reaction Conditions

Reaction Steps

To a solution of 5.8 g (16.2 mmol) 1-2 in 100 mL of pyridine was added 1.18 mL (24.3 mmol) hydrazine hydrate. The reaction was heated at 90° C. for 45 minutes, cooled to room temperature, and then to 0° C. Following the addition of 5.75 mL (80.9 mmol) of acetyl chloride, the cooling bath was removed and the reaction was stirred for 7 h. The reaction was then dumped into a separatory funnel with EtOAc and brine. The layers were separated, the organic phase was washed twice with 1M HCl, then with brine, dried over Na2SO4, and concentrated. The residue was twice dissolved in toluene and again concentrated to remove any remaining pyridine. The reside was dissolved in 100 mL of MeOH, 1.5 g (7.9 mmol) of p-toluenesulphonic acid was added, and the mixture was stirred for 2 h at room temperature. The reaction was then concentrated, the residue was dissolved in EtOAc, washed twice with a saturated solution of NaHCO3, then brine, dried over Na2CO3, and concentrated. The residue was triturated with Et2O and filtered to provide 1-3 as a white solid. Data for 1-3: LC-MS: rt=2.20 min, m/z=331 (M+1).

Provenance & Evidence