Hydrochloric Acid → N-(3-fluorophenyl)-3-[(3-hydroxyphenyl)-piperidin-4-ylidene-methyl]-N-methyl-benzamide

Participants

Reaction Conditions

Reaction Steps

Tetrahydrofuran (70 mL) and 3 N HCl (50 mL) were added to the above crude 4-([3-(tert-butyldimethylsilanyloxy)phenyl]{3-[N-(3-fluorophenyl)-N-methylcarbamoyl]phenyl}-methylene)piperidine-1-carboxylic acid tert-butyl ester (2.75 g). The resulting mixture was stirred at 60° C. for 4 h. The reaction mixture was cooled to room temperature, followed by the addition of water (100 mL). The resulting solution was extracted with diethyl ether (100 mL×2). The remaining water layer was neutralized to pH≅9. by 10% NaOH. The water layer became cloudy at this stage. The cloudy water mixture was extracted by n-butanol (100 mL×3). The combined n-butanol layers were washed by water (75 mL×2) and brine (75 mL×1), dried by Na2SO4 and concentrated to give crude product (2.27 g; crude), which was purified to give N-(3-fluorophenyl)-3-[(3-hydroxyphenyl)-piperidin-4-ylidene-methyl]-N-methyl-benzamide (579 mg). 1H NMR (600 MHz, DMSO-d6) δ 9.25 (s, 1H), 7.23 (m, 3H), 7.09 (d, 1H, J=10.0 Hz), 7.03 (dd, 1H, J=8.0, 8.0 Hz), 6.96 (ddd, 1H, J=8.5, 8.5, 2.5 Hz), 6.92 (m, 2H), 6.85 (s, 1H), 6.56 (dd, 1H, J=8.0, 2.0 Hz), 6.34 (s, 1H), 6.31 (d, 1H, J=7.5 Hz), 3.35 (s, 3H), 2.65 (m, 2H), 2.55 (m, 2H), 2.13 (bs, 1H), 2.07 (m, 2H), 1.72 (m, 2H); Found: C, 72.87; H, 6.51; N, 5.86. Calc. C, 72.77; H, 6.62; N, 5.98.

Provenance & Evidence