反应详情

3-{[(2,4-Difluorophenyl)sulfonyl]methyl}azetidine hydrochloride (60 mg, 0.21 mmol) and 2-bromo-1-(4-fluorophenyl)ethanone (52 mg, 0.23 mmol) were stirred together at room temperature with K2CO3 (90 mg, 0.65 mmol) in DMF (3 mL) under an inert atmosphere. Water was added to the mixture after 5.5 h and the mixture was then extracted with EtOAc. The organic extracts were washed with water and saturated brine then dried (MgSO4), filtered and concentrated in vacuo. The resultant material was purified using preparative thin layer chromatography on silica eluted with 50% EtOAc-isohexane to give the free base. This was then dissolved in EtOAc and treated with 1M HCl in diethyl ether. The solids was filtered off and dried in vacuo to give 2-(3-{[(2,4-difluorophenyl)sulfonyl]methyl}azetidin-1-yl)-1-(4-fluorophenyl)ethanone hydrochloride as a colourless solid (12 mg). 1H NMR (500 MHz, d6-DMSO) δ 3.09–3.19 (2H, m), 3.95 (2H, d, J=7.1 Hz), 4.01–4.16 (2H, br s), 4.17–4.29 (2H, m), 5.06 (2H, s), 7.40–7.47 (3H, m), 7.70–7.75 (1H, m), 7.91–7.94 (1H, m), 7.99–8.02 (2H, m), 10.72 (1H, br s). m/z (ES+) 384 (M+H)+.

1. extractionthe mixture was then extracted with EtOAc
2. washThe organic extracts were washed with water and saturated brine
3. dry with materialthen dried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe resultant material was purified
7. washeluted with 50% EtOAc-isohexane
8. customto give the free base
9. filtrationThe solids was filtered off
10. customdried in vacuo