Synthesis
General procedure: n-Butyl lithium (n-BuLi, 2.5 M hexane solution, 12.2 mL, 30.6 mmol) was slowly added dropwise to a solution of (methylsulfonyl)benzene (2.2 g, 13.9 mmol) in tetrahydrofuran (THF, 38 mL) at 0 °C, with the dropwise addition time being controlled at 10 minutes. After the dropwise addition, the reaction mixture was continued to be stirred for 30 minutes. Subsequently, chlorodiethylphosphonate (2.4 mL, 16.7 mmol) was added dropwise to the reaction system.After 30 min, oxetan-3-one (1.0 g, 13.9 mmol) was dissolved in THF (2 mL) and slowly added dropwise to the reaction mixture at -78 °C. After completion of the dropwise addition, the reaction mixture was stirred continuously at -78 °C for 2 hours. At the end of the reaction, the reaction mixture was diluted with aqueous ammonium chloride (NH4Cl) (100 mL) and extracted with ethyl acetate (EtOAc, 100 mL x 2). The organic layers were combined, concentrated and the residue was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate=3/1) to afford the target product 3-((phenylsulfonyl)methylene)oxetane (2.4 g, 82% yield) as a colorless oil.1H NMR (400 MHz, CDCl3): δ 7.90-7.88 (m, 2H), 7.68- 7.64 (m, 1H), 7.57 (t, J=7.6Hz, 2H), 6.13-6.11 (m, 1H), 5.66-5.64 (m, 2H), 5.30-5.27 (m, 2H).
References
[1] Patent: WO2018/137619, 2018, A1. Location in patent: Page/Page column 54; 55
[2] Journal of Medicinal Chemistry, 2010, vol. 53, # 8, p. 3227 - 3246
[3] Journal of Medicinal Chemistry, 2014, vol. 57, # 20, p. 8540 - 8562
[4] Patent: US2015/238473, 2015, A1. Location in patent: Paragraph 0271
[5] Patent: WO2013/16197, 2013, A1. Location in patent: Page/Page column 92
