Trifluoroacetic acid → 5-(2-Amino-3-trifluoromethyl-phenyl)-1-[4-(4-chloro-phenoxy)-phenyl]-pyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a mixture of 1-[4-(4-chloro-phenoxy)-phenyl]-5-hydroxy-pyrrolidin-2-one (10 mg, 0.033 mmol) and TFA (0.2 mL) in CH2Cl2 (0.8 mL) is added 3-trifluoroaniline (50 mL). After stirring at 40° C. for 14 h, the mixture is cooled and concentrated. The resulted residue is treated with saturated NaHCO3 aqueous solution (1 mL) and extracted with EtOAc (3×3 mL). The combined organic layers is concentrated and purified by preparative LC/MS to provide the title compound 5-(4-amino-3-trifluoromethyl-phenyl)-1-[4-(4-chloro-phenoxy)-phenyl]-pyrrolidin-2-one as major product (11 mg, 75%, example 2) and 5-(2-amino-3-trifluoromethyl-phenyl)-1-[4-(4-chloro-phenoxy)-phenyl]-pyrrolidin-2-one as minor product (2.52 mg, 17%, example 5). Example 2: 1H NMR (CDCl3, 400 MHz) δ 7.27 (d, 2H), 7.23 (d, 1H), 7.17 (d, 2H), 7.14 (dd, 1H), 6.89 (d, 2H), 6.88 (d, 2H), 6.71 (d, 1H), 6.02 (br, 2H), 5.14 (dd, 1H), 2.64-3.0 (m, 3H), 2.05-2.13 (m, 1H); HPLC-MS calculated for C23H18ClF3N2O2 (M+H+) 447.1, found 447.1. Example 5: 1H NMR (CDCl3, 400 MHz) δ 7.40 (d, 3H), 7.25 (d, 2H), 7.15 (d, 2H), 7.14 (dd, 1H), 6.90 (d, 2H), 6.88 (d, 2H), 6.76 (t, 1H), 5.25 (dd, 1H), 4.24 (br, 2H), 2.56-2.80 (m, 3H), 2.05-2.18 (m, 1H); HPLC-MS calculated for C23H18ClF3N2O2 (M+H+) 447.1, found 447.1.

Provenance & Evidence