Hydrochloric Acid → (2S, 4S, 5S)-5-[N-(t-Butoxycarbonyl)-3-(4-thiazolyl)-L-alanyl]amino-6-cyclohexyl-4-hydroxy-2-(1-hydroxy-1-methylethyl)-N-methylhexanamide

Participants

Reaction Steps

A mixture of 1.20 g (3.00 mmoles) of (2S, 4S, 5S)-5-(t-butoxycarbonylamino)-6-cyclohexyl-4-hydroxy-2-(1-hydroxy-1-methylethyl)-N-methylhexanamide (prepared as described in Preparation 23) in 20 ml of a 4N solution of hydrogen chloride in dioxane was stirred at room temperature for 30 minutes under an atmosphere of nitrogen. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and then diethyl ether was added to the residue. The solvent was then removed by distillation under reduced pressure from the resulting solution. The same operation was repeated in total three times, and the residue was then dried under reduced pressure for 8 hours. At the end of this time, 900 mg (3.30 mmoles) of N-(t-butoxycarbonyl)-3-(4-thiazolyl)-L-alanine were added to a suspension of the dried material in 20 ml of anhydrous tetrahydrofuran, and then 0.50 ml (3.30 mmoles) of diethyl cyanophosphate and 0.92 ml (6.60 mmoles) of triethylamine were added to the resulting mixture, whilst ice-cooling and under an atmosphere of nitrogen. The mixture was then stirred for 5 hours, after which the solvent was removed by distillation under reduced pressure, and the residue was purified by medium pressure silica gel column chromatography (using a 20:1 by volume mixture of methylene chloride and methanol as eluent), followed by recrystallization from diisopropyl ether, to give 1.51 g (yield 91%) or the title compound as white crystals, melting at 203°-205° C.

Provenance & Evidence