Synthesis
General procedure for the synthesis of 2-nitro-4-benzyloxy-5-methoxybenzoic acid from 4-(benzyloxy)-5-methoxy-2-nitrobenzaldehyde: 4-(benzyloxy)-5-methoxy-2-nitrobenzaldehyde (20 g, 69.62 mmol) was dissolved in acetone (200 mL), and preheated 10% potassium permanganate solution was added slowly at 30 °C. The reaction mixture was stirred at 50 °C for 2 h and then cooled to room temperature. Subsequently, the mixture was filtered through a diatomaceous earth pad and the filter cake was washed with acetone and a little hot water. The filtrate was concentrated under reduced pressure and cooled to 0°C. The concentrate was acidified to pH 4 with hydrochloric acid, stirred for 30 min and filtered to give a solid product of 2-nitro-4-benzyloxy-5-methoxybenzoic acid (18.5 g, 88% yield). The product was confirmed by NMR hydrogen spectrum (300 MHz, DMSO-d6): δ 13.58 (brs, 1H), 7.70 (s, 1H), 7.46-7.40 (m, 6H), 7.39 (s, 1H), 5.25 (s, 2H), 3.92 (s, 3H). Mass spectrum (ESI+, m/z): 304 [M+H]+.
References
[1] Patent: WO2012/30160, 2012, A2. Location in patent: Page/Page column 50
[2] Patent: WO2017/194960, 2017, A1. Location in patent: Page/Page column 187
[3] Patent: US4950674, 1990, A
[4] Farmaco, Edizione Scientifica, 1977, vol. 32, # 8, p. 579 - 591
[5] Tetrahedron Letters, 1986, vol. 27, # 10, p. 1149 - 1152
