Water → 1-(2-(Aminomethyl)phenyl)-5-furyl-3-trifluoromethylpyrazole

Participants

Reaction Conditions

Reaction Steps

Cobalt chloride (1.76 g, 13.6 mmol) was added to 2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzonitrile (4.12 g, 13.6 mmol) and sodium borohydride (1.03 g, 27.2 mmol) in DMF (40 mL). The reaction turned black and became warm. An ice bath was added and the reaction was stirred at 0° C. for 45 min, then at room temperature for 23 h. Additional sodium borohydride (0.25 g, 6.6 mmol) was added and the resulting mixture was stirred at room temperature for 6 h. A room temperature water bath was added, and the reaction was quenched with water (10 mL) over 10 min, then MeOH (20 mL), then 6M HCl (20 mL) over 15 min. The quenched reaction was stirred at room temperature for 16 h, diluted with EtOAc, and extracted with water and 0.1M HCl. The resulting emulsion was filtered through celite, and the organic layer was removed, dried over Na2SO4, filtered, and evaporated to yield crude product (857 mg). The aqueous layers were combined and neutralized (pH 8) with solid Na2CO3 (6.9 g). Addition of EtOAc yielded another emulsion, which was filtered through celite. The organic layer was removed, and the aqueous layer was extracted again with EtOAc. The organic layers were combined, dried over Na2SO4, filtered, and evaporated to yield a second batch of crude product (3.55 g). The two batches of crude product were combined and chromatographed on silica gel (0-10% MeOH/CHCl3) to yield the desired product (3.77 g, 90%). 1H NMR (CDCl3) δ7.59 (m, 2H), 7.38 (m, 2H), 7.33 (d, 1H, J=7.3), 6.96 (s, 1H), 6.27 (m, 1H), 5.59 (d, 1H, J=3.6), 3.51 (s, 2H).

Provenance & Evidence