Methanesulfonyl chloride → HCID 58180452, compound

Temperature

80 °C

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.

1. temperatureThe mixture is then cooled to room temperature
2. extractionextracted with dichloromethane (3×20 mL)
3. customThe organics are isolated
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. dissolutionThe residue is dissolved in dichloromethane (100 mL)
8. temperaturecooled to 0° C.
9. stirringThe mixture is stirred at room temperature for 1 hour
10. customseparated
11. dry with materialThe organic phase is dried over magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated
14. customthe crude material is purified by flash chromatography (dichloromethane/methanol gradient)

ORD record

ord-b218a3f372ee47839c1626b70f9e89e5

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08575168B2