1-(4-Fluorophenyl)-6,6-dimethoxy-1,5,6,7,8,9-hexahydrocyclohepta[f]indazole-5-carbonitrile → 1-(4-Fluorophenyl)-6-hydroxy-1,7,8,9-tetrahydrocyclohepta[f]indazole-5-carbonitrile

Participants

Reaction Steps

A solution of 1-(4-fluorophenyl)-6,6-dimethoxy-1,5,6,7,8,9-hexahydrocyclohepta[f]indazole-5-carbonitrile (28, R1=4-Fluorophenyl) (54.8 g, 141 mmol) in THF (1000 mL) and 3N aq. HCl (170 mL) was heated at reflux for about 5 h. The reaction was cooled to rt and concentrated to about 200 mL volume. The product was extracted with ether (500 mL) and EtOAc (100 mL). The organic layer was washed with water (150 mL) and sat. aq. NaCl (150 mL). The organic layer was dried over Na2SO4, filtered and concentrated to about 100 mL volume and diluted with heptane (about 100 mL). The product was filtered off and rinsed with 1:1/EtOAc:heptane (2×100 mL) and dried under vacuum at about 50° C. for about 18 h to yield 1-(4-fluorophenyl)-6-hydroxy-1,7,8,9-tetrahydrocyclohepta[f]indazole-5-carbonitrile (29, R1=4-Fluorophenyl) (23.1 g, 51%) as a solid: LC/MS, method 3, Rt=2.19 min, MS m/z 318 (M−H)—. 1H NMR (400 MHz, DMSO) δ 11.35 (s, 1H), 8.34 (s, 1H), 7.85-7.77 (m, 2H), 7.76 (s, 1H), 7.71 (s, 1H), 7.47-7.38 (m, 2H), 2.82-2.74 (m, 2H), 2.31-2.22 (m, 2H), 2.19-2.07 (m, 2H).

Provenance & Evidence