Synthesis
The general procedure for the synthesis of 2-chloro-4-cyanobenzoic acid from methyl 2-chloro-4-cyanobenzoate was as follows: lithium hydroxide (1.12 g, 26.69 mmol) was added to a dioxane/water (4:1, 100 mL) solution of methyl 2-chloro-4-cyanobenzoate (2.60 g, 13.29 mmol). The reaction mixture was stirred at room temperature for 3 h followed by vacuum concentration. The concentrated residue was partitioned between 1N hydrochloric acid and chloroform, and the organic layer was washed with brine and again concentrated under vacuum. The obtained residue was purified by recrystallization from a solvent mixture of dioxane and petroleum ether to finally obtain 2-chloro-4-cyanobenzoic acid (2.33 g, 97% yield) as a pale orange solid.
References
[1] Patent: EP1449844, 2004, A1. Location in patent: Page 24
[2] Patent: WO2013/8162, 2013, A1. Location in patent: Page/Page column 63; 64
[3] Patent: EP1512687, 2005, A1. Location in patent: Page/Page column 9-10
[4] Patent: US6511974, 2003, B1
[5] Journal of Medicinal Chemistry, 2008, vol. 51, # 24, p. 8124 - 8134
