Synthesis
Synthesis of 2,6-dimethylbenzyl alcohol: The synthesis of 2,6-dimethylbenzyl alcohol was carried out with reference to the method of Beaulieu et al. (2000) but the original method was unsuccessful, so it was changed to a different reducing agent. 2,6-dimethylbenzoic acid (1.00 g, 6.65 mmol) was suspended in anhydrous THF (10 mL) under nitrogen protection and a THF solution of BH3 (SMe2) was slowly added. The reaction mixture was heated under reflux conditions for 16 h. The reaction was subsequently quenched with saturated ammonium chloride solution (5 mL) and 2 M HCl (10 mL) (note: there was a violent gas release during the reaction). The organic layer was separated and the aqueous layer was extracted three times with ethyl acetate (45 mL each time). The organic extracts were combined, washed twice sequentially with saturated sodium bicarbonate solution (20 mL each time), dried over anhydrous Na2SO4, concentrated under reduced pressure, and finally purified by silica gel column chromatography to give 2,6-dimethylbenzyl alcohol (0.50 g, 51% yield) as a white solid.1H NMR (400 MHz, CDCl3): δ7.08 (m, 3H, Ph-H), δ7.08 (m, 3H, Ph-H), δ7.08 (m, 3H, 2H), δ7.08 (m, 3H, 2H, 2H). 4.70 (s, 2H, Ph-CH2), 4.05 (br s, 1H, OH), 2.40 (s, 6H, CH3).
References
[1] Bioorganic and Medicinal Chemistry, 1996, vol. 4, # 12, p. 2167 - 2178
[2] Patent: US2016/193181, 2016, A1. Location in patent: Paragraph 1161-1162
[3] Patent: WO2008/131368, 2008, A2. Location in patent: Page/Page column 116-117
[4] Tetrahedron, 2001, vol. 57, # 30, p. 6375 - 6382
[5] ChemMedChem, 2016, vol. 11, # 23, p. 2607 - 2620
