Synthesis
The general procedure for the synthesis of 4-(methylsulfonyl)benzyl bromide from 4-methylsulfonylphenylmethanol was as follows: methanesulfonyl chloride (1.00 mL, 12.9 mmol) was added slowly and dropwise to a stirred solution of 4-(methylsulfonyl)phenylmethanol (2.00 g, 10.7 mmol) and triethylamine (2.24 mL, 16.1 mmol) in acetone (25 mL) at 0 °C. The reaction mixture was continued to be stirred at this temperature for 30 minutes. The reaction mixture was filtered and lithium bromide (4.66 g, 53.7 mmol) was added to the filtrate in three batches at 0 °C. The resulting mixture was stirred at 0 °C for 5 minutes and then gradually warmed up to room temperature and continued stirring for 1.5 hours. The reaction mixture was filtered again and the filtrate was concentrated under vacuum. After dilution with 50 mL of water, the product was extracted with dichloromethane (50 mL x 3). The organic phases were combined, dried over anhydrous sodium sulfate and concentrated under vacuum to give 1-(bromomethyl)-4-(methylsulfonyl)benzene (2.80 g, 100% yield) as a white solid.1H NMR (300 MHz, CDCl3) δppm: 7.95 (d, J=8.4 Hz, 2H), 7.61 (d, J=8.4 Hz, 2H), 4.53 (s, 2H), 3.08 (s, 3H).
References
[1] Patent: WO2017/136871, 2017, A1. Location in patent: Paragraph 0223
[2] Journal of the Chemical Society, 1962, p. 1420 - 1427
[3] Canadian Journal of Chemistry, 1984, vol. 62, p. 2330 - 2336
[4] Journal of Medicinal Chemistry, 1989, vol. 32, # 8, p. 1757 - 1763
[5] Journal of Organic Chemistry, 2011, vol. 76, # 20, p. 8203 - 8214
