Hydrochloric Acid → 5-{N-[2(R)-Benzyl-4-oxopentanoyl]-3-(4-thiazolyl)-L-alanyl}amino-6-cyclohexyl-4-hydroxy-2-(1-hydroxy-1-methylethyl)-N-methylhexanamide

Participants

Reaction Steps

A mixture or 192 mg (0.35 mmoles) of (2S, 4S, 5S)-5-[N-(t-butoxycarbonyl)-3-(4-thiazolyl)-L-alanyl]amino-6-cyclohexyl-4-hydroxy-2-(1-hydroxy-1-methylethyl)-N-methylhexanamide [prepared as described in Example 9(a)] in 2 ml of a 4N solution of hydrogen chloride in dioxane was stirred at room temperature 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 dried by evaporation under reduced pressure for 8 hours, and was then suspended in 5 ml of anhydrous tetrahydrofuran. 86 mg (0.42 mmoles) of 2(R)-benzyl-4-oxopentanoic acid (prepared as described in Preparation 20) were then added to the suspension, after which 0.06 ml (0.40 mmoles) of diethyl cyanophosphate and 0.16 ml (1.15 mmoles) of triethylamine were added to the mixture, whilst ice-cooling and under an atmosphere of nitrogen. The mixture was then stirred for 3 hours, after which the solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (using an 8:1 by volume mixture of methylene chloride and methanol as the developing solvent), to give 164 mg (yield 74%) of the title compound as an amorphous substance.

Provenance & Evidence