Sodium Hydroxide → phenyl (3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)carbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-amine (102.9 g, 448.9 mmol) in EtOAc (1 L) at 10.9° C. was added a NaOH solution (2.5 M, 269 mL), and the biphasic reaction mixture warmed to 15.9 and then stabilized. Phenyl chloroformate (98.4 g, 156.5 mmol) was added in one portion and the temperature rose to 25.5 and then stabilized. The ice bath was removed and the reaction was monitored by HPLC. After 1 hour an additional 25 mL of 2.5 M NaOH was added. The reaction mixture was stirred overnight, and then diluted with EtOAc (200 mL). The organic layer was washed with brine (1 L), dried over Na2SO4 (200 g) and concentrated to about 400 to 500 mL of EtOAc. The concentrated solution was warmed to 60° C. After the solids had dissolved, heptane (2 L) was slowly added, during which solids formed. After stirring for 30 minutes the solid was collected via filtration and the cake was washed with 400-500 mL of heptane. The cake was dried in a vacuum oven at ambient temperature to yield 156.9 g (95.0%) of the title compound. 1H NMR (400 MHz, CDCl3) δ 7.39-7.31 (m, 6H), 7.26-7.225 (m, 2H), 7.13 (br s, 2H), 6.96 (br s, 1H), 6.47 (br s, 1H), 2.42 (s, 3H), 1.34 (s, 9H).

Provenance & Evidence