Sodium Hydroxide → (5-Bromo-1-isopropyl-1H-pyrazol-4-YL)methanol

Participants

Reaction Steps

To a solution of ethyl 5-bromo-1-isopropyl-1H-pyrazole-4-carboxylate (163 g, 0.50 mol) in 2-methyl tetrahydrofuran (400 mL) was added borane-DMS (140 mL, 1.50 mol) at 0° C., under argon (effervescence ceased after 50 mL was added). The mixture was stirred at room temperature for 30 minutes and then heated to 70° C. for 2 hours, and then to reflux for 17 hours. Additional portion of borane DMS (40 mL) was added and the mixture was stirred at reflux for an additional 3 hours. The mixture was cooled to room temperature then added gradually to ice-cold methanol (500 mL) with stirring, over a period of 30 minutes. The mixture was stirred at room temperature for 30 minutes then 2 M aqueous sodium hydroxide (1.5 L) was added. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×500 mL). The organic layers were combined, washed with brine (500 mL), dried over magnesium sulfate, filtered and the solvent removed in vacuo. The crude product was purified by dry flash chromatography (0-50% ethyl acetate in heptane) to give (5-bromo-1-isopropyl-1H-pyrazol-4-yl)methanol (70.8 g, 65% over two steps). +ESI (M+H) 220.9; 1H NMR (400 MHz, CDCl3, δ): 7.52 (s, 1H), 4.67 (m, 1H), 4.47 (s, 2H), 2.59 (br. s., 1H), 1.41 (s, 6H).

Provenance & Evidence