反应详情

温度

10 °C

A solution of 628 g (3.5 mols) of the (-)-antipode of N-methyl-ephedrine in 7.5 liters of tert.-butyl methyl ether is added dropwise to a suspension of 133 g (3.5 mols) of lithium aluminum hydride in 1.5 liters of tert.-butyl methyl ether in the course of 45 minutes at 20° C. under an argon atmosphere. Stirring is continued for 30 minutes at 40° C., after which the mixture is cooled to 10° C., and 848 g (7 mols) of N-ethyl-aniline are added in the course of 45 minutes. The mixture is stirred for a further hour at 40° C. and then cooled to -15° C., and a solution of 522 g (2 mols) of the (E)-isomer of 1-cyclohexyl-4,4-dimethyl-2-(1,2,4-triazol-1-yl)-pent-1-en-3-one in 4.7 liters of tert.-butyl methyl ether is then added dropwise in the course of 30 minutes, the temperature of the reaction mixture being kept at -10° C. to -15° C. The mixture is stirred for a further 16 hours at -15° C., and 8 liters of water are then added slowly. 3.5 liters of 10% strength aqueous hydrochloric acid are added to the resulting reaction mixture. Thereafter, the organic phase is separated off, and the aqueous phase is extracted with three times 2.5 liters of tert.-butyl methyl ether. Tbe combined organic phases are washed with twice 2 liters of water and then evaporated down under a pressure of 20 mbar. The crystalline residue which remains is stirred with cyclohexane, and the product is filtered off under suction and dried under reduced pressure at 35° C. In this manner, 466 g (87% of theory) of the (-)-antipode of (E)-1-cyclohexyl-4,4-dimethyl-3-hydroxy-2-(1,2,4-triazol-1-yl)-pent-1-ene are obtained in the form of a crystalline product.

1. stirringThe mixture is stirred for a further hour at 40° C.
2. temperaturecooled to -15° C.
3. custombeing kept at -10° C. to -15° C
4. stirringThe mixture is stirred for a further 16 hours at -15° C.
5. customThereafter, the organic phase is separated off
6. extractionthe aqueous phase is extracted with three times 2.5 liters of tert.-butyl methyl ether
7. washTbe combined organic phases are washed with twice 2 liters of water
8. customevaporated down under a pressure of 20 mbar
9. stirringThe crystalline residue which remains is stirred with cyclohexane
10. filtrationthe product is filtered off under suction
11. customdried under reduced pressure at 35° C