Synthesis
General procedure for the synthesis of 5-bromo-2-naphthalenecarboxylic acid from 2-naphthalenecarboxylic acid:
1. Preparation of 3,6-iodo-1-methoxynaphthalene [CHEMMOL-00022].
2. Preparation of 5-bromo-2-naphthalenecarboxylic acid: 2-naphthalenecarboxylic acid (50.0 g, 0.290 mol), glacial acetic acid (250 mL), bromine (15 mL, 0.291 mol), and iodine (1.3 g, 0.005 mol) were added to a flask and mixed under nitrogen protection. The mixture was heated to reflux for 35 minutes and subsequently cooled to room temperature. The resulting thick yellow mixture was stirred at room temperature for 1 hour. The mixture was filtered and the light orange solid was washed with 100 mL of filtrate. The solid was dried under vacuum at 55 °C overnight to give 55.5 g of light orange solid.
3. Slurried the above solid with 275 mL of 1N NaOH solution for 30 minutes. The solid was collected by filtration and washed with 50 mL of filtrate in three portions. The solid was air dried in a fume hood to the end of the week to yield 46.7 g of solid.
4. The solid was added to 220 mL of water, the pH was adjusted to 1.3 with the addition of concentrated hydrochloric acid (15 mL) and the mixture was stirred for 4 hours. The solid was collected by filtration and washed with 200 mL of water. The solid was dried under vacuum at 50 °C to give 37.6 g of the intermediate 5-bromo-2-naphthalenecarboxylic acid as white crystals (HPLC purity: 90%, containing 9% 2-naphthalenecarboxylic acid, 46% yield).
References
[1] Patent: US2008/58423, 2008, A1. Location in patent: Page/Page column 9
[2] Patent: US2004/6229, 2004, A1. Location in patent: Page/Page column 15
[3] Synthetic Communications, 2011, vol. 41, # 13, p. 2017 - 2024
[4] Journal of Medicinal Chemistry, 2004, vol. 47, # 8, p. 1893 - 1899
[5] Helvetica Chimica Acta, 1938, vol. 21, p. 62,65
