53086-52-5

2-(3-Bromophenyl)propanoic Acid is an intermediate in the synthesis of Ketoprofen (K200800) related compounds.

Step 1. 3-Bromophenylacetic acid (1.30 g, 6 mmol) was azeotropized with 2 mL of anhydrous toluene to remove water under nitrogen protection and cooled to room temperature. To this solution was slowly added a THF solution of sodium bis(trimethylmethylsilyl)amide (14 mL, 1N, 14 mmol). After stirring the reaction for 20 minutes at room temperature, iodomethane (0.9 g, 7 mmol) was slowly added dropwise through a constant pressure dropping funnel. After 10 min of reaction, the pH of the reaction solution was adjusted to 2 with 2N HCl solution to quench the reaction. Subsequently, the reaction mixture was extracted with ethyl acetate (EtOAc) and the organic phase was dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated to dryness under reduced pressure. Purification by fast column chromatography (silica gel, eluent gradient: dichloromethane (DCM) to DCM/EtOAc=10:1 to 4:1 to 2:1) afforded the crude 2-(3-bromophenyl)propionic acid (1.13 g, 82% yield) as a colorless oil.

[1] Patent: WO2008/39882, 2008, A1. Location in patent: Page/Page column 171
[2] Patent: WO2008/39882, 2008, A1. Location in patent: Page/Page column 171
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[4] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 23, p. 6447 - 6454
[5] Patent: WO2016/193939, 2016, A1. Location in patent: Page/Page column 41