反应详情

To a stirred solution of 1-(diphenylmethyl)-3-(4-fluorophenoxy)azetidine (Intermediate 123, 3.2 g, 9.6 mmol) in DCE (20 ml) was added dropwise 1-chloroethylchloroformate (1.6 ml, 1.5 eq). The mixture was stirred 10 min then heated to reflux for 6 h. More 1-chloroethylchloroformate was added (1.6 ml) and heating was continued for 3 h. The mixture was cooled to room temperature and concentrated under vacuum. The residue was dissolved in MeOH (20 mL) and left to stand overnight. The mixture was heated under reflux and stirred for 1 h, then cooled to room temperature and concentrated under vacuum. The residue was crystallised under diethyl ether; the solid was broken up with a spatula, filtered off—washing with diethyl ether—and dried under vacuum to give the title compound as a cream solid (1.78 g, 91%). Method B HPLC-MS: MH+ requires m/z=168 Found: m/z=168, Rt=0.69 min (92%). 1H NMR (250 MHZ, DMSO-d6) δ ppm 9.50 (2H, br s), 7.15 (2H, t), 6.89 (2H, dd), 5.03 (1H, m), 4.39 (2H, m), and 3.93 (2H, m).

1. temperaturethen heated
2. temperatureto reflux for 6 h
3. temperatureheating
4. waitwas continued for 3 h
5. concentrationconcentrated under vacuum
6. dissolutionThe residue was dissolved in MeOH (20 mL)
7. waitleft
8. waitto stand overnight
9. temperatureThe mixture was heated
10. temperatureunder reflux
11. stirringstirred for 1 h
12. temperaturecooled to room temperature
13. concentrationconcentrated under vacuum
14. customThe residue was crystallised under diethyl ether
15. filtrationfiltered
16. washoff—washing with diethyl ether—
17. customdried under vacuum