67-56-1

623-05-2

5355-17-9

Under nitrogen protection, 3.96 g (0.03 mol) of p-hydroxybenzyl alcohol (purchased from Tokyo Chemical Industry Co., Ltd.) was added to a 100 mL three-necked flask equipped with a thermometer, a three-way stopper and a magnetic stirrer, followed by 21 g of methanol (purchased from Nacalai Tesque, Inc.) and two drops of nitromethane (purchased from Nacalai Tesque, Inc.). Under stirring conditions at room temperature, 0.2 g of hydrochloric acid (purchased from Nacalai Tesque, Inc.) was slowly added dropwise, followed by continuous stirring of the reaction mixture for 5 h at 30 °C. The reaction mixture was then analyzed by HPLC. Upon completion of the reaction, HPLC analysis showed 95% area percentage of the target product 4-methoxymethylphenol. To the reaction system, 0.28 g of pyridine (purchased from Nacalai Tesque, Inc.) and 8 g of toluene (purchased from Nacalai Tesque, Inc.) were added for neutralization, followed by concentration under reduced pressure to remove methanol. To the residue 31 g of toluene and 6 g of water were added for extraction and the organic phase was washed with 5 g of water. The resulting organic layer was concentrated, cooled to below 10 °C, and the precipitated crystals were filtered and dried to give 3.53 g (yield: 80%) of colorless crystalline 4-methoxymethylphenol. It was analyzed by HPLC and its purity was 99% (excluding the solvent toluene).