Synthesis
General procedure for the synthesis of methyl 5-amino-2-methylbenzoate (41) from methyl 2-methyl-5-nitrobenzoate: 10% Pd-C (30 mg) was added to a solution of methyl 2-methyl-5-nitrobenzoate (635 mg, 3.3 mmol) in ethyl acetate (10 mL), and the mixture was stirred for 16 h at 23°C in a hydrogen atmosphere. After completion of the reaction, the mixture was filtered through a diatomaceous earth pad and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to afford the colorless oily product methyl 5-amino-2-methylbenzoate (41) (536 mg, yield >99%), Rf = 0.57 (hexane:ethyl acetate = 1:1).1H NMR (400 MHz, CDCl3): δ 7.11 (d, 1H, J = 2.5 Hz), 6.97 (d, 1H, J = 8.1 Hz), 6.69 (dd, 1H, J = 2.5 and 8.1 Hz), 3.82 (s, 3H), 3.64 (s, 2H), 2.43 (s, 3H).13C NMR (100 MHz, CDCl3): δ 168.1, 144.1, 132.3, 129.8, 129.5, 118.8, 116.7. 51.6, 20.6. MS (EI): m/z 165.20 [M]+. HRMS (EI) calculated value C9H11NO2 [M]+ 165.0790, measured value 165.0787.
References
[1] Journal of the American Chemical Society, 2003, vol. 125, # 40, p. 12074 - 12075
[2] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 10, p. 2823 - 2827
[3] Patent: WO2004/18414, 2004, A2. Location in patent: Page 110
[4] Journal of Medicinal Chemistry, 2009, vol. 52, # 16, p. 5228 - 5240
[5] Patent: US2011/269834, 2011, A1. Location in patent: Page/Page column 29
