Hydrochloric Acid → (2S, 4S, 5S)-5-[N-(t-Butoxycarbonyl)-3-(4-thiazolyl)-L-alanyl]amino-4-hydroxy-2-(1-hydroxy-1-methylethyl)-7-methyl-N-methyloctanamide

Participants

Reaction Steps

A mixture of 274 mg (0.76 mmoles) of (2S, 4S, 5S)-5-(t-butoxycarbonylamino)-4-hydroxy-2-(1-hydroxy-1-methylethyl)-7-methyl-N-methyloctanamide (prepared as described in Preparation 28) in 5 ml of a 4N solution of hydrogen chloride in dioxane was stirred at room temperature and under an atmosphere of nitrogen for 30 minutes. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure. Diethyl ether was added to the residue, and the solvent was again removed by distillation under reduced pressure. The same operation was repeated, in total, three times. The resulting residue was then dried by evaporation under reduced pressure for 8 hours, after which it was suspended in 5 ml of anhydrous tetrahydrofuran. 248 mg (0.91 mmoles) of N-(t-butoxycarbonyl)-3-(4-thiazolyl)-L-alanine were then added to the suspension, after which 0.14 ml (0.92 mmoles) of diethyl cyanophosphate and 0.23 ml (1.65 mmoles) of triethylamine were added to the 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 resulting 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 hexane to give 356 mg (yield 91%) of the title compound as a white amorphous substance.

Provenance & Evidence