[Synthesis]
Example 8A Synthesis of 3-(methylamino)phenol: 3-aminophenol (5.37 g, 49.2 mmol) was dissolved in methyl acetate (30 mL), p-toluenesulfonic acid (50 mg) was added as a catalyst, and the reaction was heated to reflux for 18 hours. Upon completion of the reaction, the volatile solvent was removed by distillation under reduced pressure. The residue was dissolved in ethyl acetate, washed sequentially with 1N HCl, saturated NaHCO3 solution and brine, dried with Na2SO4 and filtered, and the filtrate was concentrated under reduced pressure to obtain the crude product. The crude product was dissolved in tetrahydrofuran (THF, 25 mL), 1M borane tetrahydrofuran complex (27.2 mL, 27.2 mmol) of THF solution was added and the reaction was carried out for 18 h at room temperature. At the end of the reaction, the reaction was quenched by careful addition of 1N HCl and stirred for 30 min before the reaction solution was alkalized and extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over Na2SO4 and filtered and the filtrate was concentrated under reduced pressure. The residue was purified by fast chromatography (30% ethyl acetate/hexane as eluent) to afford the target compound 3-(methylamino)phenol as a viscous yellow oil (1.72 g, 28% yield). The structure of the product was confirmed by 1H NMR (300 MHz, CDCl3) and mass spectrometry (DCI/NH3): 1H NMR δ 7.03 (t, 1H), 6.13-6.24 (m, 2H), 6.11 (t, 1H), 4.54 (bs, 1H), 3.72 (bs, 1H), 2.82 (s, 3H); MS m/z 124 (M + H )+, 141 (M + NH4)+. |