تفاعل #10302

معادلة التفاعل

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

المردود 13.6%

المذيبات

EtOAc

Water

diethyl ether

DMF

ظروف التفاعل

المعالجة

1. 1
   استخلاصthe mixture was then extracted with EtOAc
2. 2
   غسيلThe organic extracts were washed with water and saturated brine
3. 3
   تجفيفthen dried (MgSO4)
4. 4
   ترشيحfiltered
5. 5
   تركيزconcentrated in vacuo
6. 6
   أخرىThe resultant material was purified
7. 7
   غسيلeluted with 50% EtOAc-isohexane
8. 8
   أخرىto give the free base
9. 9
   ترشيحThe solids was filtered off
10. 10
    أخرىdried in vacuo

الإجراء التجريبي

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)+.

المصدر