Ethyl Acetate → 1-(4-(3-Cyanopropyl)-3-fluorobenzyl)cyclobutanecarbonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(4-Amino-2-fluorophenyl)butanenitrile (71) (30 mg, 0.17 mmol), cyclobutanone (24 mg, 0.34 mmol) and trimethylsilyl cyanide (TMSCN, 33 mg, 0.34 mmol) was heated to 80° C. and stirred for 15 h. To the medium was added ethyl acetate (2×20 mL) and then washed with water (2×20 mL). The organic layer was dried over MgSO4 and concentrated and the residue was purified with silica gel column chromatography (dichloromethane:acetone, 9:1) to give 1-(4-(3-Cyanopropyl)-3-fluorobenzyl)cyclobutanecarbonitrile (70) (40 mg, 92%): 1H NMR δ 7.01 (dd, 1H, J=8.0, 7.5 Hz), 6.37 (dd, 1H, J=8.0, 2.4 Hz), 6.34 (dd, 1H, J=11.8, 2.4 Hz), 4.18 (br s, 1H), 2.76-2.81 (m, 2H), 2.70 (t, 2H, J=7.3 Hz), 2.33-2.39 (m, 2H), 2.33 (t, 2H, J=7.1 Hz) 2.12-2.30 (m, 2H), 1.90-1.95 (m, 2H).

Provenance & Evidence