4-Chloro-3-methoxybenzoic acid

Uses

4-Chloro-3-methoxybenzoic acid can be used to synthesize specific drug molecules, such as a key intermediate for the antiarrhythmic drug amiodarone.

Synthesis

B. Synthesis of 4-chloro-3-methoxybenzoic acid (0200) To crude 1-chloro-2-methoxy-4-methylbenzene (7.8 g, 50 mmol) was added an aqueous solution of potassium permanganate (KMnO4, 19.8 g, 125 mmol) (300 mL). The reaction mixture was stirred vigorously under reflux conditions for 17 h. After completion of the reaction, the filter was passed through diatomaceous earth and the filter cake was washed with hot water (200 mL). The clarified filtrate was washed with ether (2 x 150 mL) and then acidified with concentrated hydrochloric acid (HCl) to pH < 2. After addition of concentrated hydrochloric acid (9 mL), the precipitate was collected by filtration to give pure white solid 4-chloro-3-methoxybenzoic acid (5.36 g, 58% yield). Electrospray mass spectrometry (ES-MS) showed (M + H)+ peak located at m/z = 187.

References

[1] Journal of Medicinal Chemistry, 1992, vol. 35, # 23, p. 4408 - 4414
[2] European Journal of Medicinal Chemistry, 2011, vol. 46, # 12, p. 5754 - 5762
[3] Archiv der Pharmazie, 2011, vol. 344, # 11, p. 745 - 754
[4] Chemical Biology and Drug Design, 2013, vol. 82, # 3, p. 336 - 347
[5] European Journal of Medicinal Chemistry, 2013, vol. 65, p. 315 - 322