82477-67-6

124-38-9

33719-74-3

82477-67-6

The general procedure for the synthesis of 3-chloro-5-methoxybenzoic acid from carbon dioxide and 3,5-dichloroanisole is as follows: the magnesium scraps (Fluka purum used for the Grignard reaction) are first pre-treated: the scraps are placed in a glass sintered funnel, 0.1 M hydrochloric acid is added and stirred with a glass rod for a few seconds, followed by a wash with three parts water to remove the acid. Finally, the magnesium chips were washed with two parts of acetone and bottled. Next, RedAl (1 g, 70% wt. of toluene solution) was added to dry tetrahydrofuran (100 mL, 99.95%) for drying. Pretreated magnesium shavings (5 g, 200 mmol) were placed in a round-bottomed flask and rinsed three times with nitrogen. 3,5-Dichloroanisole (26 g, 146 mmol) was dissolved in dry tetrahydrofuran (100 mL) and dibromoethane (1.8 g, 10 mmol) was added. The reaction mixture was flushed with nitrogen and refluxed for 2 hours. The heating was stopped and dry ice (10 g) was added in batches over 2 min. After all the dry ice was dissolved, the reaction mixture was poured into ice containing 2 M hydrochloric acid (400 mL). Post-treatment by ether (300 mL) extraction resulted in 11.2 g of 3-chloro-5-methoxybenzoic acid, 60.2 mmol in 41% yield.1H-NMR (500 MHz; acetone-d6): δ 7.57 (m, 1H), 7.49 (m, 1H), 7.23 (m, 1H), 3.91 (s, 3H).