Diethyl Ether → HCID 86722464, compound

Participants

Reaction Steps

A flask was charged with potassium 2-methylpropan-2-olate (45.4 g, 404 mmol), Et2O (1000 mL) and methyltriphenylphosphonium bromide (141 g, 395 mmol). The mixture was stirred for about 2 h at rt then 1-(4-fluorophenyl)-7,8-dihydro-1H-pyrazolo[3,4-b]quinolin-5(6H)-one (112, R1=4-Fluorophenyl) (55.5 g, 197 mmol) was added over about 15 min. The mixture was stirred at rt for about 15 h. 1,4-Dioxane (100 mL) was added to the reaction mixture and stirring was continued for about 4 h. Solids were removed by filtration and the pad was washed with 600 mL Et2O. The filtrate was concentrated under reduced pressure then EtOAc (250 mL) and heptane (750 mL) was added. The solids were removed by filtration then the pad was washed with 3 portions of 3:1 heptane/EtOAc (100 mL). The filtrate was concentrated under reduced pressure to yield a slurry. A mixture of 3:1 heptane/EtOAc (100 mL) was added to the material then the slurry was poured onto a pad of 600 grams of silica pre-gelled with 3:1 Heptane/EtOAc. The pad was washed with 3:1 Heptane/EtOAc (6 L) until TLC (3:1 Heptane/EtOAc, visualized by UV) showed essentially no more desired product in the filtrate. The filtrate was concentrated under reduced pressure to yield 1-(4-fluorophenyl)-5-methylene-5,6,7,8-tetrahydro-1H-pyrazolo[3,4-b]quinoline (113, R1=4-Fluorophenyl) (44.0 g, 80%): LC/MS, method 3, Rt=2.87 min, MS m/z 280 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.63 (s, 1H), 8.37 (s, 1H), 8.34-8.27 (m, 2H), 7.45-7.38 (m, 2H), 5.67 (d, J=0.8 Hz, 1H), 5.09 (d, J=0.9 Hz, 1H), 3.10 (t, J=6.4 Hz, 2H), 2.63-2.56 (m, 2H), 1.97-1.87 (m, 2H).

Provenance & Evidence