Thionyl Chloride → 4-Bromo-1-(chloromethyl)-2-methylbenzene

To a solution of 4-bromo-2-methylbenzyl alcohol (9.0 g) in dichloromethane (50 mL) was added thionyl chloride (3.8 mL) under ice-cooling, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure to give 4-bromo-2-methylbenzyl chloride (9.8 g). To a suspension of sodium hydride (60%, 2.1 g) in tetrahydrofuran (90 mL) was added ethyl 4-methyl-3-oxopentanoate (7.5 g) under ice-cooling, and the reaction mixture was stirred at room temperature for 1 hour. 4-Bromo-2-methylbenzyl chloride (9.8 g) was added to the reaction mixture, and the resulting mixture was stirred at 70° C. for 3 days. The reaction mixture was poured into a saturated aqueous ammonium chloride solution, and the mixture was extracted with diethyl ether. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. To a solution of the residue in toluene (20 mL) was added hydrazine monohydrate (5.4 mL), and the mixture was stirred at 90° C. overnight. The reaction mixture was concentrated under reduced pressure, and the residue was treated with n-hexane-diethyl ether (10/1) to crystallize. The crystals were collected by filtration and washed with n-hexane, water and n-hexane successively, and dried under reduced pressure to give the title compound (12.4 g).

1. temperaturecooling
2. concentrationThe reaction mixture was concentrated under reduced pressure

ORD record

ord-3ac9ee4a603d49abbca2eb9088ec5c99

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07375087B2