Uses
Methyl 2-(3-bromophenyl)acetate is used as a reagent to synthesize the methyl ester derivative of (R)-Flurbiprofen (F598730). (R)-Flurbiprofen is a nonsteroidal anti-inflammatory drug that exists as a racemate and also has potential application as a treatment for patients with Alzheimer’s Disease.
Synthesis
General procedure for the synthesis of methyl (3-bromophenyl)acetate from methanol and 3-bromophenylacetic acid: acetyl chloride (0.08 mL, 1.2 mmol, 0.5 eq.) and 3-bromophenylacetic acid (0.5 g, 2.3 mmol, 1.0 eq.) were added to methanol (10 mL), and the reaction mixture was refluxed for 2 hours. Upon completion of the reaction, the consumption of starting material was confirmed by TLC monitoring. The reaction mixture was concentrated and extracted with dichloromethane (DCM). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford methyl (3-bromophenyl)acetate as a colorless oil (0.525 g, 98.7% yield). The product was analyzed by LC-MS (ES), m/z = 229.0, 231.0 [M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 3.61 (s, 3H), 3.70 (s, 2H), 7.26-7.30 (m, 2H), 7.43-7.46 (m, 1H), 7.48 (s, 1H).
References
[1] Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 13, p. 2843 - 2866
[2] Journal of Medicinal Chemistry, 2008, vol. 51, # 3, p. 392 - 395
[3] Patent: EP1479681, 2004, A1. Location in patent: Page 111; 112
[4] Patent: US2007/3539, 2007, A1. Location in patent: Page/Page column 96
[5] Journal of Medicinal Chemistry, 1995, vol. 38, # 26, p. 4976 - 4984
