Synthesis
General procedure for the synthesis of (2-amino-4-methoxyphenyl)methanol from 3-methoxy-2-nitrobenzyl alcohol: to a solution of commercially available 4-methoxy-2-nitrobenzoic acid (4.0 g, 20.66 mmol) in tetrahydrofuran (20 mL) was added N-methylmorpholine (2.2 mL, 20 mmol) at -15 °C and under nitrogen protection followed by the addition of chloroformic acid in portions of isobutyl chloroformate (2.6 mL, 20 mmol). After 5 min of reaction, the reaction mixture was filtered and the solid was washed with tetrahydrofuran (20 mL). The filtrate was cooled to -15 °C and aqueous sodium borohydride (3M, 10 mL) was added to it. After stirring the reaction for 5 minutes, the reaction mixture was partitioned between water and dichloromethane and the aqueous layer was extracted with dichloromethane (3 x 100 mL). The organic layers were combined, washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was redissolved in tetrahydrofuran (35 mL), palladium-carbon catalyst (10%, 400 mg) was added, and the reaction was stirred under hydrogen atmosphere for 18 hours. Upon completion of the reaction, the reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with hexane/ethyl acetate (3:2) as eluent to give 744 mg (24% yield) of the target product as a yellow solid.1H-NMR (DMSO-d6) δ: 3.63 (s, 3H); 4.30 (s, 2H); 4.84-4.96 (m, 2H); 6.08 (dd, 1H); 6.20 (d 1H); 6.90 (d, 1H).
References
[1] Synlett, 2017, vol. 28, # 14, p. 1724 - 1728
[2] Patent: WO2006/134378, 2006, A1. Location in patent: Page/Page column 110
