Synthesis
Example 25B Synthesis of 5-cyano-2-methoxybenzoic acid: Example 25A (methyl 5-cyano-2-methoxybenzoate, 6.1 g, 31.9 mmol) and lithium hydroxide monohydrate (5.36 g, 128 mmol) were reacted in a solvent mixture of tetrahydrofuran (100 mL) and water (50 mL) with stirring for 3 hours at room temperature. Upon completion of the reaction, the pH of the reaction solution was adjusted to 3 with 3N hydrochloric acid, followed by two solvent extractions with a mixture of isopropanol/dichloromethane (1:3, v/v). The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give 5.6 g (99% yield) of the target product 5-cyano-2-methoxybenzoic acid. The product was characterized by 1H NMR (500 MHz, deuterated chloroform), δppm: 4.15 (s, 3H), 7.17 (d, J=8.85 Hz, 1H), 7.86 (dd, J=8.85,2.44 Hz, 1H), 8.47 (d, J=2.14 Hz, 1H).
References
[1] Patent: US2008/287510, 2008, A1. Location in patent: Page/Page column 25
[2] Patent: WO2010/54024, 2010, A2. Location in patent: Page/Page column 74
[3] Patent: WO2008/130953, 2008, A2. Location in patent: Page/Page column 57-58
[4] Patent: US2008/242654, 2008, A1. Location in patent: Page/Page column 36
[5] Patent: EP1698618, 2006, A1. Location in patent: Page/Page column 78-79
