تفاعل #10301
ord-1c558c163b0846259c1e384d3e1982e0
معادلة التفاعل
المتفاعلات
الكواشف
المذيبات
ظروف التفاعل
المعالجة
- 1درجة الحرارةwas heated
- 2درجة الحرارةat reflux for 5 h under an inert atmosphere
- 3أخرىThe cooled reaction mixture
- 4أخرىwas partitioned between EtOAc and water
- 5غسيلThe EtOAc extracts were washed with water and saturated brine
- 6تجفيفthen dried (MgSO4)
- 7ترشيحfiltered
- 8تركيزconcentrated in vacuo
- 9أخرىThe resultant material was purified by column chromatography on silica
- 10غسيلeluted with a gradient of 0–15% MeOH-EtOAc
- 11أخرىto give the free base
- 12أخرىThe solvents was removed in vacuo
الإجراء التجريبي
A stirred mixture of 3-{[(4-fluorophenyl)sulfonyl]methyl}azetidine hydrochloride (150 mg, 0.56 mmol), 2-butanone (5 mL), potassium carbonate (0.25 g, 1.81 mmol), sodium iodide (20 mg, 0.13 mmol) and 4-chloro-1-(4-fluorophenyl)butan-1-one (115 μL, 0.68 mmol) was heated at reflux for 5 h under an inert atmosphere. The cooled reaction mixture was partitioned between EtOAc and water. The EtOAc extracts were washed with water and saturated brine then dried (MgSO4), filtered and concentrated in vacuo. The resultant material was purified by column chromatography on silica eluted with a gradient of 0–15% MeOH-EtOAc to give the free base. This was dissolved in EtOAc and treated with 1M HCl in diethyl ether. The solvents was removed in vacuo to give 1-(4-fluorophenyl)-4-(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)butan-1-one hydrochloride as a white solid (16 mg). 1H NMR (400 MHz, CD3OD) δ 1.90–1.99 (2H, m), 3.17 (2H, t, J=6.6 Hz), 3.25–3.35 (3H, m), 3.68 (2H, d, J=7.3 Hz), 4.0–4.2 (2H, br s), 4.2–4.4 (2H, br s), 7.20–7.27 (2H, m), 7.39–7.46 (2H, m), 7.98–8.04 (2H, m), 8.05–8.10 (2H, m). m/z (ES+) 394 (M+H)+.