반응 #10302

반응 방정식

HCl

3-{[(2,4-Difluorophenyl)sulfonyl]methyl}azetidine hydrochloride

2-bromo-1-(4-fluorophenyl)ethanone

K2CO3

→

2-(3-{[(2,4-difluorophenyl)sulfonyl]methyl}azetidin-1-yl)-1-(4-fluorophenyl)ethanone hydrochloride

수율 13.6%

용매

EtOAc

Water

diethyl ether

DMF

반응 조건

후처리

1. 1
   추출the mixture was then extracted with EtOAc
2. 2
   세척The organic extracts were washed with water and saturated brine
3. 3
   건조then dried (MgSO4)
4. 4
   여과filtered
5. 5
   농축concentrated in vacuo
6. 6
   기타The resultant material was purified
7. 7
   세척eluted with 50% EtOAc-isohexane
8. 8
   기타to give the free base
9. 9
   여과The solids was filtered off
10. 10
    기타dried in vacuo

실험 절차

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)+.

출처