R(+) Mosher acid 1.856g (99%ee, Aldrich, 7.926mmol) and pentafluorophenol 2.188g (11.89mmol, 1.5eq.) solution in anh. acetonitrile 12mL was cooled on ice bath. Solid DCC 1.635g (7.926mmol) was added in one portion and the mixture was stirred at 0C for 1h, the cooling bath was removed and continued at ambient temperature for 14 hours (overnight). The precipitated dicyclohexyl urea was removed by flitration, washed with acetonitrile and discarded. The combined filtrates were evaporated and the obtained semi-solid residue was dried on highvac for 6 hours to remove excess of pentafluorophenol. The crude product was dissolved in hexane 10mL, the cloudy solution was filtered through a 2g-plug of silica, the silica plug was washed with cyclohexane 30mL. The combined filtrates were evaporated and the residue was dried on highvac (for 1 hour). The residue was dissolved in hexane 15mL, allowed to crystallize in freezer for 10 hours (-20C overnight). The supernatants were decanted, the crystalline product quickly rinsed with freezer-cooled hexane (2x5mL) and dried on highvac while cold. Y=2.601g (82%) of large white crystals
The Pfp-ester of Mosher acid is a non-hygroscopic solid that can be stored at room temperature. It is used as an inexpensive and stable alternative to Mosher acid chloride. The OH acylation with the Pfp ester is typically done in a concentrated DMF solution, with DMAP as a base. This protocol is suitable for derivatization without purification – just the DMF is evaporated by stream of nitrogen before the NMR analysis. The pentafluorophenyl signals in the 19-F spectra are far to the left so they do not interfere with the Mosher CF3 group signals. Unreacted Mosher acid Pfp ester signals can be used as internal standard.