تفاعل #10305

معادلة التفاعل

3-Bromomethyl-6-fluoro-1,2-benzisothiazole

3-{[(4-fluorophenyl)sulfonyl]methyl}azetidine hydrochloride

potassium carbonate

→

title compound

المردود 23.2%

6-Fluoro-3-[(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)methyl]-1,2-benzisothiazole hydrochloride

المردود 23.2%

المذيبات

DMF

sodium hydroxide

ظروف التفاعل

المعالجة

1. 1
   استخلاصextracted with EtOAc (2×10 mL)
2. 2
   غسيلThe organic extracts were washed with saturated brine (10 mL)
3. 3
   تجفيفdried (MgSO4)
4. 4
   تركيزconcentrated
5. 5
   أخرىThe residue was purified by preparative thin layer chromatography
6. 6
   غسيلeluting with 2.5% MeOH/DCM
7. 7
   أخرىto afford an oil which
8. 8
   أخرىcrystallised
9. 9
   workup.DISSOLUTIONThe solid was dissolved in EtOAc
10. 10
    درجة الحرارةthe resulting solution heated
11. 11
    workup.ADDITIONtreated with 1M HCl in diethyl ether (0.11 mL)
12. 12
    درجة الحرارةto cool
13. 13
    أخرىto give a crystalline solid which
14. 14
    أخرىwas collected under suction

الإجراء التجريبي

3-Bromomethyl-6-fluoro-1,2-benzisothiazole (73 mg, 0.3 mmol) was added to a mixture of 3-{[(4-fluorophenyl)sulfonyl]methyl}azetidine hydrochloride (57 mg, 0.21 mmol) and potassium carbonate (91 mg, 0.66 mmol) in DMF (2 mL) and the resulting mixture stirred at room temperature for 18 h. The mixture was diluted with 0.5M sodium hydroxide solution (20 mL) and extracted with EtOAc (2×10 mL). The organic extracts were washed with saturated brine (10 mL), combined, dried (MgSO4) and concentrated. The residue was purified by preparative thin layer chromatography, eluting with 2.5% MeOH/DCM, to afford an oil which crystallised on standing (35 mg, 41%). The solid was dissolved in EtOAc, the resulting solution heated and treated with 1M HCl in diethyl ether (0.11 mL). The mixture was allowed to cool to give a crystalline solid which was collected under suction to afford the title compound (21 mg). 1H NMR (400 MHz, CD3OD) δ 3.33–3.41 (1H, m), 3.72 (2H, d, J=7.6 Hz), 4.23–4.28 (2H, m), 4.44–4.49 (2H, m), 4.96 (2H, s), 7.35–7.46 (3H, m), 7.87–7.90 (1H, m), 7.99–8.04 (2H, m), 8.10–8.13 (1H, m). (471 MHz, CD3OD)δF −105.2, −112.7. m/z (ES+) 395 (M+H)+.

المصدر