Ethyl Acetate → 3',5'-Dichloro-4'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-carboxylic acid methyl ester

Participants

Reaction Steps

Dissolve trifluoro-methanesulfonic acid 3,5-dichloro-4-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-phenyl ester (5 g, 10.54 mmol) in 50 mL toluene, add aqueous 2 M sodium carbonate and evacuate/purge with nitrogen 3 times. Add p-carboxymethylphenylboronic acid (2.85 g, 15.81 mmol), degas again, then add Pd(PPh3)4 (1.22 g, 1.05 mmol). Degass/purge one more time then reflux overnight. Separate layers, wash the organic layer with water twice, then wash with brine. Dry over sodium sulfate, filter and concentrate under vacuum to yield a brown foam. Add ethyl acetate to get a tan solid and filter to get 3.8 g product. Concentrate the filtrate to recover 0.4 g more product after purification via silica gel chromatography using 25% ethyl acetate: MS (m/z): 460 (M+).

Provenance & Evidence