3096-81-9

107622-80-0

The general procedure for the synthesis of 4-phenoxybenzylamine from 4-phenoxybenzonitrile was as follows: 4-phenoxybenzonitrile (200 mg, 1.00 mmol) was dissolved in 8 mL of methanol, and 5% Pd/C catalyst (0.2 equiv, 400 mg) was added. The reaction was stirred under hydrogen atmosphere for 3 h. The reaction was filtered through diatomaceous earth after completion. The filtrate was purified by preparative thin layer chromatography (pTLC) to afford 4-phenoxybenzylamine as a white solid (179 mg, 88% yield) using a dichloromethane solution containing 10% methanol and 2% triethylamine as an unfolding agent. Subsequently, compound 42 (1.1 eq., 22 mg) was dissolved in toluene and 2,5-dimethoxyaniline (1 eq., 8 mg), BINAP (0.3 eq., 11 mg), Pd(OAc)2 (0.15 eq., 2 mg), and Cs2CO3 (2.5 eq., 46 mg) were added and the mixture was stirred and reacted for 15 hr at 105 °C. At the end of the reaction, the solvent was removed under reduced pressure and the crude product was purified by silica gel column chromatography using ethyl acetate as eluent. Finally, the compound was further purified by preparative thin layer chromatography (pTLC) using hexane solution containing 50% ethyl acetate as the unfolding agent to afford compound 34 as a colorless oil (12.4 mg, 48% yield).