General procedure for the synthesis of 4-pyrazol-1-ylbenzyl alcohol from methyl 4-(1H-pyrazol-1-yl)benzoate:
G) Synthesis of [4-(1H-pyrazol-1-yl)phenyl]methanol
To a solution of ethyl 4-(1H-pyrazol-1-yl)benzoate (73.7 g) in tetrahydrofuran (THF, 500 mL), sodium borohydride (19.5 g) and calcium chloride (56.8 g) were slowly added under cooling in an ice bath. The reaction mixture was stirred at room temperature for 16 h, followed by heating and refluxing for 2 days. After completion of the reaction, the reaction mixture was diluted with 1N hydrochloric acid and extracted with ethyl acetate (4 times). The organic layers were combined, washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was removed by concentration under reduced pressure and the residue was washed with tert-butyl methyl ether to give 4-pyrazol-1-ylbenzyl alcohol (49.6 g) as a white solid.
Product characterization: 1H NMR (400 MHz, CDCl3) δ 2.79 (1H, br s), 4.68 (2H, s), 6.45 (1H, t, J = 2.0 Hz), 7.38 (2H, d, J = 7.6 Hz), 7.61 (2H, d, J = 8.4 Hz), 7.70 (1H, s), 7.89 (1H, d, J = 1.6 Hz).
