Synthesis
General procedure for the synthesis of 6-methoxy-1H-benzo[d][1,3]oxazine-2,4-dione from 2-amino-5-methoxybenzoic acid: 5-methoxy-o-toluic acid (30 g, 179 mmol) was dissolved in a mixture of water (1.2 L) and concentrated hydrochloric acid. Triphosgene (63.8 g, 215 mmol) was then added, followed by concentrated hydrochloric acid (15 mL). The reaction mixture was stirred at room temperature for 3-4 hours until the reaction was complete (monitored by thin layer chromatography on silica gel plates). Upon completion of the reaction, a white solid precipitated from the solution. The solid was collected by filtration and washed with a large amount of water (4 L). The resulting solid was dried under vacuum to afford anhydride (30.7 g) of 89% purity in the following yield: melting point 237-239 °C; 1H NMR (300 MHz, CDCl3) δ 3.65 (s, 3H), 7.11 (d, 1H, J=8.9 Hz), 7.35 (dd, 1H, J=8.9 Hz, 2.7 Hz), 7.19 (d, 1H J=2.7 Hz), 11.61 (bs, 1H). The spectral data were in agreement with the values reported in the literature [27]. The product can be used directly in the next step of the reaction without further purification. Note: Triphosgene is toxic and requires extra care when handling.
References
[1] Journal of Medicinal Chemistry, 2016, vol. 59, # 4, p. 1492 - 1500
[2] Organic Process Research and Development, 2013, vol. 17, # 8, p. 1042 - 1051
[3] European Journal of Medicinal Chemistry, 2017, vol. 126, p. 550 - 560
