Thionyl Chloride → 4-Chloro-2-(chloromethyl)-1-methoxybenzene

To a solution of (5-chloro-2-methoxy-phenyl)-methanol (17.1 g, 99.1 mmol) in methylene chloride (100 mL) was added thionyl chloride (14.5 mL, 198 mmol). The reaction was stirred at reflux for 3 hours, cooled to room temperature and concentrated in vacuo. The crude product was dissolved in methylene chloride and washed with saturated aqueous sodium hydrogen carbonate then dried over magnesium sulfate. Concentration in vacuo gave 4-chloro-2-chloromethyl-1-methoxy-benzene (18.4 g). To a solution of 4-chloro-2-chloromethyl-1-methoxy-benzene (18.4 g, 96.4 mmol) in acetonitrile (100 mL) was added potassium cyanide (12.5 g, 193 mmol) and 18-crown-6 (2.54 g, 9.64 mmol). The reaction was stirred 12 hours at ambient temperature, diluted with ethyl acetate and washed with aqueous sodium hydrogen carbonate. The organic layer was dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by passing it through a pad of silica gel, eluting with methylene chloride to give the title compound (17.2 g).

1. temperatureat reflux for 3 hours
2. concentrationconcentrated in vacuo
3. dissolutionThe crude product was dissolved in methylene chloride
4. washwashed with saturated aqueous sodium hydrogen carbonate
5. dry with materialthen dried over magnesium sulfate
6. concentrationConcentration in vacuo

ORD record

ord-315781d7513349d9ae7a1576522627d3

Source dataset

uspto-grants-2005_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06974817B2