Synthesis
General procedure for the synthesis of (2-amino-4-nitrophenyl)methanol from 2-amino-4-nitrobenzoic acid: 2-amino-4-nitrobenzoic acid (1.00 g, 5.49 mmol) was dissolved in tetrahydrofuran (THF, 20 mL) at room temperature. Borane-tetrahydrofuran complex (BH3-THF, 21.96 mL, 21.96 mmol) was added slowly and dropwise through the addition funnel. The reaction mixture was stirred continuously for 12 hours at room temperature. Upon completion of the reaction, the mixture was cooled in an ice bath and methanol (100 mL) was slowly added to quench the reaction. Subsequently, the reaction mixture was concentrated and the residue was transferred to a split funnel containing saturated aqueous sodium bicarbonate solution (50 mL). The aqueous layer was extracted with ether (3 x 75 mL). The organic layers were combined, washed with brine (50 mL), dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated. The residue was suspended in water, filtered and dried to give (2-amino-4-nitrophenyl)methanol (650 mg, 70% yield) as an orange solid. The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 7.46 (d, J = 2.0 Hz, 1H), 7.38-7.35 (m, 2H), 5.57 (s, 2H), 5.34 (t, J = 5.4 Hz, 1H), 4.43 (d, J = 5.5 Hz, 2H).
References
[1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 19, p. 5810 - 5831
[2] Patent: WO2015/6100, 2015, A1. Location in patent: Page/Page column 113
[3] Journal of Medicinal Chemistry, 2006, vol. 49, # 17, p. 5080 - 5092
[4] Patent: US2003/195201, 2003, A1
[5] Journal of Organic Chemistry, 2010, vol. 75, # 20, p. 7033 - 7036
