Methyl iodide → 2-Chloro-5-[1,4-dimethyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]-4-fluorobenzoic acid

Participants

Reaction Conditions

Reaction Steps

A solution of 30 g of 5-[4-bromo-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]-2-chloro-4-fluorobenzoic acid in 800 mL of anhydrous THF was stirred with a mechanical stirrer and treated with 3.36 g of 80% NaH. The stirred mixture was kept under a nitrogen atmosphere and heated to 60° C. for one hour. After formation of the sodium carboxylate salt, the mixture was cooled to -110° C. and 32.3 mL of 2.5M n-butyllithium in hexanes was added never allowing the temperature to exceed -100° C. The reaction was stirred at -110° C. for ten minutes, subsequently treated with 9.3 mL of methyl iodide and allowed to warm to room temperature. The mixture was quenched with 3N HCl and the volatiles removed. A precipitate formed which was collected and recrystallized from ethanol/water to give 24.5 g of a white solid: mp 155.0° C.; 1HNMR (CDCl3) δ 2.06 (m, 3H), 4.01 (s, 3H), 7.27 (d, 1H, J=9.6 Hz), 8.17 (d, 1H, J=7.6 Hz). Anal. Calcd for C13H9O2Cl1N2F4 : C, 46.38; H, 2.69; N, 8.32. Found: C, 46.46; H, 2.65; N, 8.33.

Provenance & Evidence