Synthesis
Preparation procedure of 1-(Diphenylmethyl)-3-azetidinyl methanesulfonate: To a reaction flask was charged 632 g (2.64 mol) of 1-benzhydrylazetidin- 3-ol, acetonitrile (1.9 L), and triethylamine (601 g, 1.5 equiv). The mixture was cooled in an ice-acetone bath (-5 °C). Methanesulfonyl chloride (436 g, 1.20 equiv) was added via a drop funnel while keeping the reaction temperature at less than5 °C. HPLC showed reaction completion after 15 min. Water (6.3 L) was added, and the reaction mixture was stirred for 2 h at room temperature and filtered. The filter cake was rinsed with water (2 x 1 L), pulled dry under vacuum, and directly subjected to the amination reaction in the next step. Yield 100%.
References
[1] Patent: US2005/54697, 2005, A1. Location in patent: Page/Page column 78
[2] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 4, p. 1084 - 1088
[3] Patent: WO2011/61214, 2011, A1. Location in patent: Page/Page column 85-86
[4] Patent: US2014/288045, 2014, A1. Location in patent: Paragraph 0605
[5] Patent: WO2016/44772, 2016, A1. Location in patent: Paragraph 319
