Ammonia → Methyl[3-cyano-5-(trifluoromethyl)benzyl]{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl[3-iodo-5-(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (Example 119, 508 mg, 0.76 mmol) in DMF (40 mL) was added CuCN (1.7 g, 19.0 mmol). The reaction was stirred at 100° C. for 30 hours. The reaction was poured into aq. NH3 (40 mL) and extracted with EtOAc (3×40 mL). All the collected organic extracts were washed with brine (40 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 5% to 80% EtOAc/hexanes afforded methyl[3-cyano-5-(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate. Rf=0.55 (20% EtOAc/hexanes). LCMS=565.3 (M+1)+. 1H NMR (C6D6, 500 MHz, 70° C.) δ 7.63 (s, 1H), 7.43-7.38 (m, 3H), 7.17-7.13 (m, 3H), 6.86 (s, 1H), 6.74 (d, J=8.5 Hz, 1H), 4.37 (broad singlet, 2H), 4.08 (broad singlet, 2H), 3.45 (s, 3H), 3.40 (s, 3H), 2.80 (m, 1H), 1.18 (d, J=7.0 Hz, 6H).

Provenance & Evidence