反应详情

温度

2.5 °C

Aluminum chloride (4.40 g) is added to tetrahydrofuran (100 mL) at 25-30° C. The solution is cooled to 0-5° C. and a solution of lithium aluminum hydride (1.80 g) in tetrahydrofuran (19 mL) is added. The mixture is stirred for 15-30 minutes. A solution of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrol-1-one (10.0 g) in tetrahydrofuran (200 mL) is added by drops at 0-5° C. and the mixture is maintained for 1 hour. Sodium hydroxide solution (0.6N, 120 mL) is added at 0 to 5° C. The mixture is extracted with ethyl acetate (240 mL) and layers are separated, then the aqueous layer is washed with ethyl acetate (80 mL). The combined organic layer is washed with saturated brine solution (2×160 mL). The organic layer is dried over anhydrous sodium sulfate (10 g) and the solvent from the organic layer is evaporated at 45° C. The obtained residue is dissolved in 1-propanol (30 mL) at 25-30° C. This solution is added to a solution of maleic acid (5.3 g) in 1-propanol (20 mL) at 25-30° C. The mixture is stirred at 25-35° C. for 24 hours and the obtained solid is collected by filtration, washed with 1-propanol (5 mL), and dried under reduced pressure at 46° C., to afford 6.2 g of the title compound. PXRD pattern: complies with a reference pattern of monoclinic polymorph.

1. temperaturethe mixture is maintained for 1 hour
2. extractionThe mixture is extracted with ethyl acetate (240 mL) and layers
3. customare separated
4. washthe aqueous layer is washed with ethyl acetate (80 mL)
5. washThe combined organic layer is washed with saturated brine solution (2×160 mL)
6. dry with materialThe organic layer is dried over anhydrous sodium sulfate (10 g)
7. customthe solvent from the organic layer is evaporated at 45° C
8. dissolutionThe obtained residue is dissolved in 1-propanol (30 mL) at 25-30° C
9. additionThis solution is added to a solution of maleic acid (5.3 g) in 1-propanol (20 mL) at 25-30° C
10. stirringThe mixture is stirred at 25-35° C. for 24 hours
11. filtrationthe obtained solid is collected by filtration
12. washwashed with 1-propanol (5 mL)
13. customdried under reduced pressure at 46° C.