Potassium Phosphate, Tribasic → (R)-1-[4-(4-chlorophenoxy)phenyl]-5-[3-(trifluoromethyl)phenyl]pyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a 10 mL reaction tube fitted with a screw cap is charged with (R)-5-[3-(trifluoromethyl)phenyl]pyrrolidin-2-one (90 mg, 0.39 mmol) and 1,4-dioxane (3 mL). 1-(4-iodophenoxy)-4-chlorobenzene (157 mg, 0.47 mmol) is then added, followed by copper iodide (15 mg, 0.078 mmol), N,N′-1,2-trans-dimethylcyclohexane-1,2-diamine (11.2 mg, 0.078 mmol), and K3PO4 (167 mg, 0.78 mmol). The system is degassed with argon then sealed and heated to 110° C. for 28 h. The reaction is cooled to room temperature, dissolved in ethyl acetate and washed with water and brine. The organic phase is dried over Na2SO4, filtered and concentrated in vacuo. Purification on silica gel (0-30% ethyl acetate in hexane) gave (R)-1-[4-(4-chlorophenoxy)phenyl]-5-[3-(trifluoromethyl)phenyl]pyrrolidin-2-one as a slightly yellow oil (102 mg, 60%). 1H NMR (CDCl3) δ (ppm) 7.60-7.50 (m, 1H), 7.49-7.37 (m, 3H), 7.34-7.28 (m, 2H), 7.27-7.21 (m, 2H), 6.91-6.67 (m, 4H), 5.28 (dd, J=6.8, 5.6 Hz, 1H), 2.84-2.59 (m, 3H), 2.07-1.94 (m, 1H). HPLC-MS calculated for C23H17ClF3NO2 (M+H+) 432.09, found 432.10.

Provenance & Evidence