Synthesis
General procedure for the synthesis of ethyl 5-phenyl oxazole-2-carboxylate from ethyl [2-phenyl-2-oxoethyl]amino-2-oxoacetate: ethyl [2-phenyl-2-oxoethyl]amino-2-oxoacetate (16.5 g, 71 mmol) was dissolved in 200 mL of anhydrous toluene in a 1 L Parr reactor. To this solution 21 mL (225 mmol, 3.15 equiv) of phosphorus oxychloride (POCl3) was slowly added. The Parr reactor was sealed and the reaction mixture was heated in an oil bath at 110°C for 48 hours. Upon completion of the reaction, the solvent and the remaining phosphorous trichloride were removed by distillation under reduced pressure to give a brown oil. To this oily substance was added 300 mL of water, followed by extraction of the aqueous phase twice with 150 mL of dichloromethane. The organic phases were combined, dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure. The resulting brown solid was recrystallized by 50 mL of ethanol to give a final 12.5 g of orange solid product in 80% yield. The product was identified by 1H NMR (300 MHz, DMSO-d6): δ 8.10 (s, 1H), 7.82 (d, J = 7.5 Hz, 2H), 7.55 (m, 3H), 4.43 (q, J = 7.1 Hz, 2H), 1.35 (t, J = 7.1 Hz, 3H). The mass spectrum (APCI+) showed m/z 218 ([M+H]+).
References
[1] Patent: WO2004/18428, 2004, A1. Location in patent: Page 362
[2] Patent: WO2005/61510, 2005, A1. Location in patent: Page/Page column 17
[3] European Journal of Medicinal Chemistry, 2015, vol. 101, p. 334 - 347
[4] Yakugaku Zasshi, 1956, vol. 76, p. 307
[5] Chem.Abstr., 1956, p. 13874
