反应详情

A solution of 1.70 g (5.8 mmol) of the azide of example 17 in 50 mL benzene was treated with 4.46 g (34.8 mmol) of 1,1-diethoxy-2-propyne followed by warming at reflux for 18 h. The solution was treated with 1.0 g (7.80 mmol) of 1,1-diethoxy-2-propyne followed by warming at reflux for an additional 3 h. The solution was cooled and concentrated in vacuo to afford an oil which was chromatographed over 200 g of 230-400 mesh silica gel, eluting with 2-3% (v/v) methanol in dichloromethane to afford 2.0 g (80%) of (S)-N-[[3-[3-Fluoro-4-(4-(diethoxymethyl)-1H-1,2,3-triazol-1-yl)phenyl]-2-oxo-5-oxazoldinyl]methyl]acetamide and (S)-N-[[3-[3-Fluoro-4-(5-(diethoxymethyl)-1H-1,2,3-triazol-1-yl)phenyl]-2-oxo-5-oxazoldinyl]methyl]acetamide as an inseparable mixture of isomers. Of this material, 410 mg (0.973 mmol) was dissolved in 10 mL THF and treated with 1 mL of 1N HCl solution followed by stirring at ambient temperature for 48 h, and then warming at reflux for 1 h. The mixture was dissolved in ethyl acetate and extracted with water. Drying (Na2SO4) and concentration in vacuo afforded an oil which was subjected to radial chromatography on a 2 mm chromatotron plate eluting with 7% (v/v) methanol in dichloromethane. The less polar fraction [110 mg (33%)] from the chromatography proved to be the title compound, isolated as a white solid. 1H NMR (CDCl3) δ 8.60, 7.99, 7.85, 7.36, 6.1, 4.86, 4.12, 3.89, 3.72, 2.04.

1. temperatureby warming
2. temperatureat reflux for 18 h
3. temperatureby warming
4. temperatureat reflux for an additional 3 h
5. temperatureThe solution was cooled
6. concentrationconcentrated in vacuo
7. customto afford an oil which
8. customwas chromatographed over 200 g of 230-400 mesh silica gel
9. washeluting with 2-3% (v/v) methanol in dichloromethane