Acetone → (3S, 5S)-5-[(1S)-1-(N-t-Butoxycarbonylamino)-2-cyclohexylethyl]-3-(1-hydroxy-1-methylethyl)dihydrofuran-2(3H)-one

Participants

Reaction Steps

15.81 ml (25.3 mmole) of butyllithium (as a 1.6M solution in hexane) were added, at -78° C. and under an atmosphere of nitrogen, to a solution of 3.55 ml (25.3 mmole) of diisopropylamine in 30 ml of anhydrous tetrahydrofuran, and the mixture was stirred for 30 minutes. A solution of 3.58 g (11.5 mmole) of (5S)-5-[(1S)-1-(t-butoxycarbonyl)amino-2-cyclohexylethyl]dihydrofuran-2(3H)-one in 10 ml of anhydrous tetrahydrofuran was then added to the mixture, and the mixture was stirred at -78° C. for 1 hour. 1.86 ml (25.3 mmole) of acetone purified by distillation was added to the mixture, after which the mixture was stirred for a further 2 hours. At the end of this time, the reaction mixture was mixed with a saturated aqueous solution of ammonium chloride and extracted with ethyl acetate. The organic layer was washed, in turn, with a 10% w/v aqueous solution of citric acid, with water and with a saturated aqueous solution of sodium chloride, after which it was dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure and the residue was purified by medium pressure column chromatography through silica gel (using a 1:1 by volume mixture of hexane and diethyl ether as the eluent). The title compound, obtained from the less polar fractions, was isolated as white crystals, melting at 123°-125° C., and the amount obtained was 3.65 g (yield 86%).

Provenance & Evidence