Step B: Synthesis of 4-amino-5-cyano-2-hydroxy-3-methylbenzoic acid; LiOH-H2O (8.4 g, 0.2 mol) was dissolved in a mixed solvent of ethanol/water (1:1, 300 mL) at room temperature, followed by addition of ethyl 4-amino-5-cyano-2-hydroxy-3-methylbenzoate (22 g, 0.1 mol). The reaction mixture was heated to 80 °C and refluxed for 4 hours. After completion of the reaction, the mixture was concentrated under reduced pressure and the residue was diluted with 100 mL of water and washed with petroleum ether/ethyl acetate (1:1, 2 x 200 mL). The aqueous layer was separated and the pH was adjusted to 5 with 1.5 N HCl and the precipitated solid product was collected by filtration. The aqueous layer was further extracted with ethyl acetate (2 × 300 mL), the organic phases were combined, dried and concentrated to give additional product. All products were combined and washed with petroleum ether solution of 5% ethyl acetate to give pure target compound (19 g, yield >95%).TLC detection conditions: methanol/chloroform (1:4), Rf=0.2.
