Following a procedure similar to that described in Example 1, a mixture of 260 mg (0.62 mmoles) of (3S, 5S)-5-[(1S)-1-(N-t-butoxycarbonylamino)-3-methylbutyl]-3-(1-hydroxy-1-methylethyl)dihydrofuran-2(3H)-one (prepared as described in Preparation 9) in 5 ml of a 4N solution of hydrogen chloride in dioxane was stirred at room temperature for 30 minutes. At the end of this time, the solvent was removed by distillation under reduced pressure, and diethyl ether was added to the residue. The solvent was then again removed by distillation under reduced pressure. This operation was repeated in total three times, after which the residue was dried under vacuum for 8 hours. At the end of this time, the dried material was suspended in 5 ml of anhydrous tetrahydrofuran, and 187 mg (0.69 mmoles) of N-(t-butoxycarbonyl)-3-(4-thiazolyl)-L-alanine were added to the resulting suspension, followed by 0.11 ml (0.73 mmoles) of 95% diethyl cyanophosphate and 0.19 ml (1.36 mmoles) of triethylamine, all whilst ice-cooling and under an atmosphere of nitrogen. The mixture was then stirred for 6 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), to give 303 mg (yield 85%) of the title compound as an amorphous substance.
