Synthesis
General procedure for the synthesis of 2-chloro-3,4-dihydroxybenzoic acid from 2-chloro-3,4-dimethoxybenzoic acid:
Example 1; Synthesis of Compound (I-1); Step (1) 2-chloro-3,4-dimethoxybenzoic acid (Compound 1) -> 2-chloro-3,4-dihydroxybenzoic acid (Compound 2).
A dichloromethane (100 mL) suspension of 2-chloro-3,4-dimethoxybenzoic acid (10.83 g, 50 mmol) was cooled to 0 °C and then boron tribromide (BBr3, 18.91 mL, 200 mmol) was added slowly and dropwise over 15 min. The reaction mixture was continued to be stirred at 0 °C for 15 minutes, then brought to room temperature and stirred for 3 hours. Upon completion of the reaction, the mixture was slowly poured into a 2 M hydrochloric acid solution containing ice, and ethyl acetate (AcOEt) and tetrahydrofuran (THF) were added to promote layering. After removal of dichloromethane by evaporation under reduced pressure, the organic layer was separated. The organic layer was sequentially washed twice with water and once with saturated brine and then dried over anhydrous magnesium sulfate (MgSO4). After filtration to remove the desiccant, the filtrate was concentrated and dried under vacuum to afford 2-chloro-3,4-dihydroxybenzoic acid (Compound 2) as a light orange powder (5.46 g, 58% yield).
References
[1] Patent: EP2341053, 2011, A1. Location in patent: Page/Page column 42-43
[2] Yakugaku Zasshi, 1956, vol. 76, p. 1122,1125
[3] Chem.Abstr., 1957, p. 3505
