Diisopropylethylamine → (4R,5S)-4-[3,5-bis(trifluoromethyl)phenyl]-1-{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-5-methylimidazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

A solution of (1R,2S)-1-[3,5-bis(trifluoromethyl)phenyl]-N2-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}propane-1,2-diamine (8.0 mg, 0.0135 mmol) in CH2Cl2 (2 mL) was cooled to 0° C. and DIPEA (14 μL, 0.081 mmol) was added followed by triphosgene (2 mg, 0.00657 mmol). The reaction was stirred at 0° C. for 30 min and then diluted with EtOAc (30 mL). The reaction was washed with saturated NaHCO3 (10 mL) and brine (10 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography with 40% EtOAc/hexanes afforded (4R,5S)-4-[3,5-bis(trifluoromethyl)phenyl]-1-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-5-methylimidazolidin-2-one. Rf=0.24 (40% EtOAc/hexanes). LCMS=619.2 (M+1)+. 1H NMR (CD2Cl2, 600 MHz; atropisomers present) δ 6.91-7.84 (m, 9H), 3.84-4.94 (m, 4H), 3.64-3.80 (m, 4H), 2.88 (m, 1H), 1.18-1.26 (m, 6H), 0.27-0.42 (m, 3H).

Provenance & Evidence