5-(Chloromethyl)-3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazole → 3-(4-Fluorophenyl)-1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)pyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To 3-(4-fluorophenyl)pyrrolidin-2-one (0.106 g, 0.592 mmol; Example 189B) as suspension in tetrahydrofuran (0.5 mL) was added potassium t-butoxide (1.0 Min tetrahydrofuran) (0.651 mL, 0.651 mmol) dropwise at room temperature. After stirring for 15 minutes, 5-(chloromethyl)-3-(4-(trifluoromethyl)phenyl)-1,2,4-oxadiazole (0.171 g, 0.651 mmol) was added dropwise as a solution in tetrahydrofuran (0.5 mL). The reaction was heated to 50° C. for 1 hour. The reaction was concentrated, loaded onto silica gel SF15-12 g (Analogix®) and the product eluted using a gradient of 5% to 50% ethyl acetate/hexanes over 30 minutes (Flow rate=30 mL/minute) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ 8.21 (d, J=8.1, 2H), 7.76 (d, J=8.2, 2H), 7.39-7.23 (m, 2H), 7.17-6.97 (m, 2H), 4.96 (d, J=17.0, 1H), 4.84 (d, J=16.5, 1H), 3.78 (t, J=8.9, 1H), 3.74-3.59 (m, 2H), 2.77-2.57 (m, 1H), 2.25 (ddt, J=8.0, 12.9, 20.7, 1H); MS (ESI+) m/z 406.1 (M+H)+.

Provenance & Evidence