反应详情

温度

0 °C

Aluminum chloride (6.9 kg) is added in portions to tetrahydrofuran (100 L) at 0° C. Stirring is continued and a 10% solution of lithium aluminum hydride in tetrahydrofuran (35.0 L) is added keeping the temperature below 10° C. The mixture is cooled to 0° C. and stirred for 15 minutes. A solution of trans-11-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrol-1-one (IV) (10.0 kg) in tetrahydrofuran (100 L) is added to the mixture while keeping the temperature below 15° C. Tetrahydrofuran (5 L) is added, stirring is continued for 1 hour at 10° C., and 0.6 N sodium hydroxide solution (100 L) is added keeping the temperature below 10° C. Stirring is continued for 15 minutes at 20° C. and toluene (150 L) and of water (100 L) are added. Stirring is continued for 15 minutes at 20° C. and the salt layer is separated. The salt layer is extracted with toluene (2×50 L). The combined filtrates are separated and the aqueous layer is extracted with of toluene (50 L). The combined organic layers are evaporated in vacuum at 70° C. to give trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrole (A) (9.4 kg, 99%); 1H-NMR (400.13 MHz in CDCl3 relative to TMS) δ 2.54 (s, 3H), 3.15 (m, 2H), 3.25 and 3.61 (2×M, 4H), 7.01-7.36 (m, 7H).

1. customthe temperature below 10° C
2. stirringstirred for 15 minutes
3. customthe temperature below 15° C
4. stirringstirring
5. customthe temperature below 10° C
6. stirringStirring
7. waitis continued for 15 minutes at 20° C.
8. stirringStirring
9. waitis continued for 15 minutes at 20° C.
10. customthe salt layer is separated
11. extractionThe salt layer is extracted with toluene (2×50 L)
12. customThe combined filtrates are separated
13. extractionthe aqueous layer is extracted with of toluene (50 L)
14. customThe combined organic layers are evaporated in vacuum at 70° C.