1107663-03-5

Example 25 Synthesis of ethyl 2-iodo-1,3-oxazole-4-carboxylate: 2.00 g (12.81 mmol) of ethyl 2-amino-1,3-oxazole-4-carboxylate was added to 48 ml of acetonitrile solution containing 8.00 g (38.43 mmol) of p-toluenesulfonic acid dihydrate at 0°C. Subsequently, 1.77 g (25.62 mmol) of sodium nitrite and 5.32 g (32.02 mmol) of potassium iodide dissolved in 7.2 ml of water were added dropwise to the cooled suspension. The reaction mixture was stirred at 0°C for 10 minutes before slowly warming to room temperature and continued stirring overnight. After completion of the reaction, the mixture was diluted with 200 ml of water and the pH was adjusted to 9.24 with 1 M aqueous sodium bicarbonate solution. 1 ml of 2 M sodium thiosulfate solution was added to quench the reaction. The aqueous phase was extracted three times with 30 ml of ethyl acetate, the organic phases were combined and dried with anhydrous magnesium sulfate. After filtration, the solvent was removed by rotary evaporator. The crude product was purified by column chromatography on silica gel 60 (mobile phase gradient: cyclohexane/ethyl acetate 300:1→2:1) to give 0.97 g of the target compound in 28% yield.LC-MS (Method 6): retention time Rt = 1.41 min; MS (ESIpos): m/z = 268 [M + H]+.

[1] Journal of the American Chemical Society, 2010, vol. 132, # 30, p. 10286 - 10292
[2] Patent: US2011/130377, 2011, A1. Location in patent: Page/Page column 24