Acetaldehyde → HCID 86722324, compound

Participants

Reaction Conditions

Reaction Steps

A three necked round bottom flask with septum, nitrogen line, thermometer and stir bar was charged with the 1-(4-fluorophenyl)-5,7,8,9-tetrahydrocyclohepta[f]indazol-6(1H)-one (6, R1=4-Fluorophenyl) (3.75 g, 12.74 mmol) and THF (50 mL). The solution was cooled to about −70° C. then LiHMDS (12.74 mL, 12.74 mmol) was added keeping the internal temp below about −60° C. The mixture was warmed to about 0° C. over about 5 min then cooled to about −70° C. Acetaldehyde (0.786 g, 17.84 mmol) was added in one portion. The mixture was stirred for about 2 h at about −78° C. then the cold bath was removed and the mixture was allowed to warm to about 10° C. Brine (25 mL), water (25 mL) and EtOAc (100 mL) were added and the layers were separated. The aqueous layer was extracted with EtOAc (50 mL) then the organic solutions were combined, extracted with brine (50 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified on silica gel (120 g) using a gradient of 0-50% EtOAc in heptane. Product fractions were combined and concentrated under reduced pressure to yield (E)-5-ethylidene-1-(4-fluorophenyl)-5,7,8,9-tetrahydrocyclohepta[f]indazol-6(1H)-one (3.23 g, 79%); LC/MS, method 3, Rt=2.68 min, MS m/z 321 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.36 (d, J=0.8 Hz, 1H), 7.87-7.80 (m, 2H), 7.75 (s, 1H), 7.70 (s, 1H), 7.50-7.40 (m, 2H), 7.12 (q, J=7.4 Hz, 1H), 2.82 (t, J=7.0 Hz, 2H), 2.28 (t, J=7.1 Hz, 2H), 2.01-1.91 (m, 2H), 1.87 (d, J=7.4 Hz, 3H).

Provenance & Evidence