Reaction Steps
A solution of (3R,4aR,12bR)-12b-ethyl-3-ethynyl-9-(4-fluorophenyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol (11, R1=4-Fluorophenyl, R2=Ethyl, R3=Ethynyl) (0.0331 g, 0.082 mmol) and THF (1.00 mL) was added to 10 wt % Pd/C (wet) (0.006 g). The mixture was placed under a hydrogen atmosphere using a balloon. After about 2 h, the hydrogen was evacuated. The mixture was filtered through Celite® rinsing with DCM (20 mL). The organic volatiles were removed under reduced pressure. The residue was purified on silica gel (4 g) using a gradient of 0-4% EtOAc in DCM. The fractions containing product were combined and concentrated under reduced pressure. The residue was dissolved in MeCN and MeOH, treated with water, and concentrated under reduced pressure to remove the organic volatiles. The mixture was frozen then lyophilized to afford (3R,4aR,12bR)-3,12b-diethyl-9-(4-fluorophenyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol (11, R1=4-Fluorophenyl, R2=Ethyl, R3=Ethyl) (0.031 g, 91%) as an ivory solid. LC/MS, method 2, Rt=3.07 min, MS m/z 407 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.25 (s, 1H), 7.87 (s, 1H), 7.84-7.74 (m, 2H), 7.54 (s, 1H), 7.45-7.35 (m, 2H), 4.03 (s, 1H), 3.24-3.12 (m, 1H), 2.98-2.86 (m, 1H), 2.20-2.03 (m, 2H), 2.03-1.92 (m, 1H), 1.91-1.62 (m, 4H), 1.61-1.20 (m, 8H), 0.83 (t, J=7.3 Hz, 3H), 0.37 (t, J=7.1 Hz, 3H). Sign of rotation is positive.
