N-((1,1-dimethylethoxy)carbonyl)-beta-alanine → [(5S)-3-(5-{2-Fluoro-4-[(5R)-2-oxo-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-3-yl]phenyl}pyridin-2-yl)-4,5-dihydroisoxazol-5-yl]methyl beta-alaninate

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Reaction Steps

(5R)-3-(3-Fluoro-4-{6-[(5S)-5-(hydroxymethyl)-4,5-dihydroisoxazol-3-yl]pyridin-3-yl}phenyl)-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one (Example 1, 0.25 g, 0.57 mmol), N-(tert-butoxycarbonyl)-β-alanine (0.27 g, 1.43 mmol), 4-dimethylaminopyridine (0.02 g, 0.16 mmol), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride 0.25 g, 1.30 mmol) were combined in DMF (4 ml). The suspension was allowed to stir for one hour at room temperature resulting in a clear solution. The mixture was then diluted with ethyl acetate, washed with water, and dried over magnesium sulfate. The residue obtained upon filtration and evaporation was purified via chromatography (silica gel, 1% to methanol in dichloromethane). Evaporation of the product containing fractions and trituration of the resulting solid with hexane:dichloromethane (5:1) yielded the tert-butoxycarbonyl derivative of the title compound as a waxy off-white solid (0.34 g). This protected derivative was dissolved in methylene chloride (5 ml) and trifluoroacetic acid (10 ml) was added. The resulting light yellow solution was stirred at room temp. for 1 hour, then concentrated in vacuo. The residue was suspended in dioxane (20 ml), and treated with 4M HCl in dioxane (2 ml). The resulting thick suspension was stirred for 10 minutes, diluted with ether, and filtered to yield the hydrochloride salt of the title compound as a hygroscopic yellow solid (0.30 g), mp68–75° C.

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