Synthesis
The general procedure for the synthesis of 2-bromo-4-ethylphenol from 4-ethylphenol was as follows: bromine (11.6 mL, 0.23 mol) was slowly added dropwise to a cooled solution of 4-ethylphenol (25 g, 0.21 mol) in dichloromethane (125 mL) at 0°C. After the dropwise addition was completed, the reaction mixture was continued to be stirred for 5 min, followed by quenching the reaction with 1N NaOH solution. The reaction mixture was diluted with water and the organic and aqueous layers were separated. The organic layer was concentrated to give an orange colored oil. Purification by fast column chromatography (eluent: hexane/ethyl acetate, 0 to 5% gradient) afforded 2-bromo-4-ethylphenol (42 g, 98% yield) as a clear oil. The product was characterized by 1H NMR (400 MHz, CDCl3): δ 1.20 (t, J = 7.6 Hz, 3H), 2.58 (q, J = 7.5 Hz, 2H), 5.36 (s, 1H), 6.93 (d, J = 8.3 Hz, 1H), 7.03 (d, J = 8.3 Hz, 1H), 7.28 (s, 1H).
References
[1] Patent: WO2004/74270, 2004, A2. Location in patent: Page 348
[2] Patent: US2005/176701, 2005, A1. Location in patent: Page/Page column 169-170
[3] Australian Journal of Chemistry, 2003, vol. 56, # 11, p. 1099 - 1106
[4] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 24, p. 6908 - 6917
[5] Chemistry - A European Journal, 2018, vol. 24, # 62, p. 16516 - 16520
