Hydrochloric Acid → 3-(4-Fluoro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene

Participants

Reaction Conditions

Reaction Steps

To a 2.2 L Parr hydrogenation flask was added {2-[4-[1,3]dioxolan-2-ylmethyl-5-(4-fluoro-phenyl)-1-isopropyl-1H-pyrazol-3-yl]-ethyl}-carbamic acid benzyl ester (90.0 g, 0.193 mol), t-amyl alcohol (910 mL), and 3 N HCl (190 mL, 0.570 mol). The flask was charged with N2(g) and 10% Pd/C (22.2 g) was added. The reaction mixture was hydrogenated at 40 psi and at 45° C. for 18 h. The mixture was filtered through acid-treated, low metal filter paper. The filtrate was concentrated to oil, diluted with water (500 mL), and washed with EtOAc (3×250 mL). The aqueous mixture was cooled to 0° C. and basified to pH 13-14 by the addition of KOH pellets. The aqueous solution was extracted with EtOAc (3×250 mL). The combined organic layers were filtered through acid-treated filter paper. The filtrate was dried (Na2SO4) and concentrated to give the title compound. MS (ESI): exact mass calcd. for C16H20FN3, 273.16; m/z found, 274.3 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.25-7.20 (m, 2H), 7.18-7.13 (t, J=8.6, 2H), 4.28-4.21 (sept, J=6.6, 1H), 3.04-3.01 (m, 2H), 2.94-2.88 (m, 4H), 2.46 (t, J=5.2, 2H), 1.40 (d, J=6.6, 6H).

Provenance & Evidence