3-bromo-5-methylbenzoic acid

Chemical Properties

Off-white powder

Uses

3-Bromo-5-methylbenzoic Acid is an intermediate used to synthesize quinoline amide derivatives as novel VEGFR-2 inhibitors

Synthesis

1-bromo-3,5-dimethylbenzene (15 g, 81 mmol, 1.0 eq) in a mixture of pyridine (133 mL) and H2O (83 mL) was heated to 80°C. KMnO4 (25.6 g, 162 mmol, 2.0 eq) was added in portions over 45 min. After the addition was completed, heating was continued at 80°C for 1.5 h. The hot solution was then filtered, and the filtrate was acidified by addition of concentrated hydrochloric acid. The aqueous solution was extracted with EtOAc and the combined organic extracts washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (CH2Cl2 : MeOH, 80:1 to 40:1) to give 3-bromo-5-methylbenzoic acid. White solid, yield (5.2 g, 29 %). LC-MS: m/z 212.9, 215 [M+H]+. 1H NMR (400 MHz, MeOD) δ 7.91 (s, 1H), 7.79 (s, 1H), 7.57 (s, 1H), 2.38 (s, 3H).

References

[1] Patent: US2009/203657, 2009, A1. Location in patent: Page/Page column 53
[2] Patent: US2009/203677, 2009, A1. Location in patent: Page/Page column 56
[3] Patent: US2009/197871, 2009, A1. Location in patent: Page/Page column 55-56
[4] Patent: WO2009/100169, 2009, A1. Location in patent: Page/Page column 136