Pyridine → 4-(2-{[bis(benzyloxy)phosphoryl]oxy}ethyl)-2-methoxyphenyl (1R,2S)-1-[3,5-bis(trifluoromethyl)phenyl]-2-((tert-butoxycarbonyl){[4'-fluoro-5'-propyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amino)propyl carbonate

Participants

Reaction Conditions

Reaction Steps

Pyridine (0,037 mL, 0.455 mmol) was added dropwise to a stirred solution of dibenzyl 2-(4-hydroxy-3-methoxyphenyl)ethyl phosphate (195 mg, 0.455 mmol) and triphosgene (49.3 mg, 0.166 mmol) in dry CH2Cl2 (4 mL) at 0° C. under N2. The reaction was stirred at 25° C. for 1.5 h. A solution of tert-butyl {(1S,2R)-2-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-1-methylethyl}{[4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (INTERMEDIATE 7, 162.0 mg, 0.228 mmol) in dry CH2Cl2 (2 mL) was added via cannula followed by dropwise addition of pyridine (0.041 mL, 0.512 mmol). The reaction was stirred at 25° C. for 3 h. The reaction was diluted with water (15 mL) and extracted with EtOAc (3×20 mL). The combined extracts were dried (MgSO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Biotage Horizon, 25M, Si, ˜20 mL/min, 100% hexanes for 144 mL, gradient to 50% EtOAc in hexanes over 2394 mL) to give 4-(2-{[bis(benzyloxy)phosphoryl]oxy}ethyl)-2-methoxyphenyl (1R,2S)-1-[3,5-bis(trifluoromethyl)phenyl]-2-((tert-butoxycarbonyl){[4′-fluoro-5′-propyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amino)propyl carbonate, as a colorless oil. Rf=0.63 (50% EtOAc/hexanes). LCMS calc.=1166.4; found=1166.4 (M+H)+.

Provenance & Evidence