反应详情

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)+.

1. extractionextracted with EtOAc (2×10 mL)
2. washThe organic extracts were washed with saturated brine (10 mL)
3. dry with materialdried (MgSO4)
4. concentrationconcentrated
5. customThe residue was purified by preparative thin layer chromatography
6. washeluting with 2.5% MeOH/DCM
7. customto afford an oil which
8. customcrystallised
9. dissolutionThe solid was dissolved in EtOAc
10. temperaturethe resulting solution heated
11. additiontreated with 1M HCl in diethyl ether (0.11 mL)
12. temperatureto cool
13. customto give a crystalline solid which
14. customwas collected under suction