tert-Butyl 4-(chloromethyl)benzoate

1642-81-5

865-47-4

121579-86-0

The general procedure for the synthesis of tert-butyl 4-chloromethylbenzoate from 4-chloromethylbenzoic acid and potassium tert-butoxide was as follows: oxalyl chloride (101 mL) was slowly added dropwise over 30 min to a suspension of dichloromethane (1.2 L) containing 5 mL of 4-chloromethylbenzoic acid (181.8 g) in DMF. After the dropwise addition, the reaction mixture was stirred at room temperature for 24 hours. Subsequently, the solvent was removed by concentration under reduced pressure and co-evaporated with toluene for further drying. To the residue was added 908 mL of methyl tert-butyl ether (MTBE) and the mixture was cooled to -5°C. At this temperature, a tetrahydrofuran (THF) solution of potassium tert-butoxide (1.0 M, 1172 mL) was added dropwise while ensuring that the internal temperature of the reaction did not exceed 10°C. After completion of the dropwise addition, stirring of the reaction mixture was continued for 1 hour. Subsequently, the reaction mixture was treated with 500 mL of saturated sodium bicarbonate solution and after stirring for 5 minutes, the organic phase was separated. The organic phase was washed with saturated sodium chloride solution and dried with magnesium sulfate. Finally, 241.7 g (86% yield) of tert-butyl 4-chloromethylbenzoate was obtained by concentration as a dark colored oil. Its 1H NMR (CDCl3) data were as follows: δ 1.59 ppm (s, 9H), 4.61 (s, 2H), 7.45 (d, 2H), 7.99 (d, 2H).