Methanesulfonyl chloride → HCID 58180452, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 3-hydroxyazetidine hydrochloride A6a (1.4 g, 14.8 mmol) and 4-trifluoromethylbenzaldehyde (1.98 mL, 14.8 mmol) in dichloroethane (50 mL) is treated with ethyldiisopropylamine (2.56 mL, 14.8 mmol) and heated to 80° C. for 1 hour. The mixture is then cooled to room temperature and sodium triacetoxyborohydride (6.2 g, 29.6 mmol) is added and the mixture is stirred at room temperature for 16 hours. The reaction is treated with saturated sodium hydrogencarbonate solution e (50 mL), and extracted with dichloromethane (3×20 mL). The organics are isolated and dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue is dissolved in dichloromethane (100 mL), cooled to 0° C. and treated with ethyldiisopropylamine (3.3 mL, 19.2 mmol) and methanesulfonyl chloride (1.5 mL, 19.2 mmol). The mixture is stirred at room temperature for 1 hour, diluted with saturated sodium bicarbonate (50 mL) and separated. The organic phase is dried over magnesium sulfate, filtered, concentrated and the crude material is purified by flash chromatography (dichloromethane/methanol gradient) to afford 1-(4-(trifluoromethyl)benzyl)azetidin-3-yl methanesulfonate A6b: 1H-NMR (CDCl3, 400 MHz) δ 7.51 (d, J=8.0 Hz, 2H), 7.32 (d, J=8.0 Hz, 2H), 5.04 (m, 1H), 3.69 (m, 2H), 3.67 (s, 2H), 3.22 (m, 2H), 2.95 (s, 3H); MS calcd. for C12H15F3NO3S ([M+H]+): 310.1, found: 310.1.

Provenance & Evidence