Chemical Properties
White low melting crystalline solid
Synthesis
Procedure for the synthesis of 4-bromo-3-methylbenzyl alcohol: Methyl 4-bromo-3-methylbenzoate (2.0 g, 8.7 mmol) was dissolved in anhydrous THF (10 mL) and slowly added to a pre-cooled suspension of lithium aluminum hydride (400 mg, 10.4 mmol) in anhydrous THF (30 mL). After addition, the reaction mixture was allowed to gradually warm up to room temperature with continuous stirring for 3 hours. Upon completion of the reaction, water (0.4 mL), 15% NaOH aqueous solution (0.4 mL), and water (1.2 mL) were added sequentially to quench the excess lithium aluminum hydride under the cooling of an ice bath. Insoluble material was removed by diatomaceous earth filtration and the solid residue was washed with ethyl acetate (20 mL x 5). The filtrates were combined and washed with saturated saline (50 mL) and subsequently dried over anhydrous sodium sulfate. The solvent was removed by concentration under reduced pressure to afford the crude product 4-bromo-3-methylbenzyl alcohol (1.6 g, 100% yield), which could be used in the subsequent reaction without further purification.1H-NMR (CDCl3, 400 MHz) data were as follows: δ 7.53 (1H, d, J = 8.1 Hz), 7.26 (1H, d, J = 1.5 Hz), 6.40 (1H, dd, J = 8.1, 1.5 Hz). = 8.1, 1.5 Hz), 4.68 (2H, s), 2.44 (3H, s).
References
[1] Patent: US2014/51863, 2014, A1. Location in patent: Paragraph 0205; 0256-0257
[2] Patent: WO2011/143426, 2011, A1. Location in patent: Page/Page column 51
[3] Patent: US2013/131016, 2013, A1. Location in patent: Paragraph 0190
[4] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 1, p. 66 - 71
[5] Journal of Medicinal Chemistry, 2006, vol. 49, # 13, p. 3774 - 3789
