Potassium Hydroxide → 5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-carboxamide

Participants

Reaction Steps

A solution of 5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-carbonitrile (727 mg, 2.28 mmol) and KOH (767 mg, 13.7 mmol) in H2O (7.70 mL) and i-PrOH (11.55 mL) was subjected to microwave irradiation (300 W 130° C., 4 h) in a sealed tube. The reaction mixture was concentrated in vacuo to remove the i-PrOH. The aqueous slurry obtained was diluted with water (50 mL) and extracted with EtOAc (50 mL). The organic extract was dried (Na2SO4) and concentrated in vacuo to afford 5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-carboxamide. The aqueous layer was acidified with concentrated HCl and extracted with EtOAc (3×50 mL). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo to give 5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-carboxylic acid as a colorless solid. 1H NMR (CDCl3, 500 MHz) δ 8.01 (s, 1H), 7.71 (d, J=7.8 Hz, 1H), 7.41 (d, J=7.8 Hz, 1H), 7.14 (d, J=8.1 Hz, 1H), 7.04 (s, 1H), 6.77 (d, J=8.1, 1H), 3.68 (s, 3H), 2.84 (septet, J=6.7 Hz, 1H), 1.19 (d, J=6.7 Hz, 6H).

Provenance & Evidence