455-38-9

102940-86-3

General procedure for the synthesis of 2-chloro-3-fluorobenzoic acid from m-fluorobenzoic acid: 1. 3-Fluorobenzoic acid (4.02 g, 28.71 mmol) was dissolved in 20 mL of tetrahydrofuran (THF) to prepare a solution. 2. the above solution was slowly added dropwise to a suspension containing tetramethylene diamine (TMEDA) (10.00 mL, 66.3 mmol) and 1.3 M sec-butyllithium (sec-BuLi) (48 mL, 62.4 mmol) at -90 °C. the solution was then dissolved in 20 mL of tetrahydrofuran (THF) to form a solution. 3. 50 mL of THF was added to dilute the reaction mixture, maintaining the temperature at -90°C with continuous stirring for 35 minutes. 4. The reaction mixture was slowly warmed to -78°C followed by the addition of a solution of hexachloroethane (27.0 g, 113.9 mmol) in 50 mL of THF. 5. After the reaction had proceeded for 20 h, the reaction was quenched with water and the reaction mixture was diluted with ether. 6. The pH of the reaction mixture was adjusted to 1-2 using concentrated hydrochloric acid (HCl) to promote stratification. 7. The organic layer was separated, washed sequentially with water and brine, then dried and concentrated to give 30.4 g of crude product (tan solid). 8. The crude product was washed with hexane to yield 3.728 g (74% yield) of the target product 2-chloro-3-fluorobenzoic acid (1a) as a light tan solid. Mass spectrometry (MS) analysis showed m/z 175.2 (M + H).