反应详情

To a suspension of 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepine-5(4H)-thione in 100 ml of toluene was added 11.49 g (0.11 mole) N-methylaniline and the mixture heated to reflux with stirring for 2 days (after approx. 6 hr, 23.0 g (0.22 mole) additional N-methylaniline was added). Toluene was removed by rotary evaporation (90° C., water aspirator). The N-methylaniline was removed also by rotary evaporation (90° C., vacuum pump). The residue was taken up in 100 ml of chloroform and washed with 3×30 ml dilute aqueous sodium hydroxide. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated by rotary evaporation (80° C., water aspirator). More N-methylaniline was removed with the vacuum pump at 90° C. for several hours. To the residue was added 150 ml of ethyl acetate at which point some product crystallized out. However, since much remained in solution, preparative HPLC on a silica gel column eluting with 60% hexane/40% ethyl acetate was effected. After concentrating the flasks containing the product, crystallization was effected induced by seeding. The chromatographed product was recrystallized from ethyl acetate/isopropyl alcohol and amounted to 1.1 g m.p. 164°-5° C. Approximately 2 g additional was collected by recrystallization of crude product, m.p. 163°-4° C. The combined yield was 3.1 g (26%).

1. temperaturethe mixture heated
2. temperatureto reflux
3. customToluene was removed by rotary evaporation (90° C., water aspirator)
4. customThe N-methylaniline was removed also by rotary evaporation (90° C., vacuum pump)
5. washwashed with 3×30 ml dilute aqueous sodium hydroxide
6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated by rotary evaporation (80° C., water aspirator)
9. customMore N-methylaniline was removed with the vacuum pump at 90° C. for several hours
10. additionTo the residue was added 150 ml of ethyl acetate at which point some product
11. customcrystallized out
12. washeluting with 60% hexane/40% ethyl acetate
13. concentrationAfter concentrating the flasks
14. additioncontaining
15. customthe product, crystallization
16. customThe chromatographed product was recrystallized from ethyl acetate/isopropyl alcohol
17. customApproximately 2 g additional was collected by recrystallization of crude product, m.p. 163°-4° C