反应详情

温度

2.5 °C

A solution of chloromagnesium-cyclopropylacetylide (CPA-MgCl) was prepared by adding neat cyclopropyl acetylene (3.62 gms) to a stirred solution of n-butyl magnesium chloride (2M solution in tetrahydrofuran, 26.8 ml) at 0-5° C. The solution was stirred for another 2 hours at 0-5° C. Step B: In another dry flask, to anhydrous tetrahydrofuran (80 ml) at 0-5° C., sodium hydride (57% dispersion in mineral oil, 4.71 gms) was added slowly. The mixture was stirred for 30 minutes at 25° C. to 30° C. and again cooled to 0° C. to 5° C. (1R,2S)-Pyrrolidinyl norephidrine (13.5 gms) and 2,2,2-trifluoroethanol (4.3 gm) were added and stirred for 60 minutes at 25° C. to 30° C. To the reaction mixture, was added a solution of zinc bromide (12 gms) in tetrahydrofuran (40 ml) and stirred for 60 minutes at 25° C. to 30° C., to obtain ephedrine zincate complex. The solution of chloromagnesium-cyclopropylacetylide of Step A was then added to the ephedrine zincate complex at 25° C. to 30° C. and stirred for 2 hours at the same temperature. To the resultant reaction mass was added 4-chloro-2-trifluoroacetyl aniline (10 gms) at 25° C. to 30° C. and the mixture was stirred 15 hours at same temperature. After completion of the reaction, the reaction mixture was quenched with 30% aqueous potassium carbonate (5.5 ml) and the solid precipitate was filtered. The filtrate was taken and partially concentrated and then toluene (100 ml) added followed by washed with 30% citric acid solution in water (50 ml). The organic layer was partially concentrated and hexane (50 ml) was added. The mixture was cooled to 0° C., filtered and the solid precipitate was washed with chilled hexane (10 ml). The wet product was dried at 50° C. to 55° C. under reduced pressure to afford the title compound. Yield: 10 gms.

1. stirringThe mixture was stirred for 30 minutes at 25° C. to 30° C.
2. additionwere added
3. stirringstirred for 60 minutes at 25° C. to 30° C
4. stirringstirred for 60 minutes at 25° C. to 30° C.
5. customto obtain ephedrine zincate complex
6. stirringstirred for 2 hours at the same temperature
7. customTo the resultant reaction mass
8. stirringthe mixture was stirred 15 hours at same temperature
9. customAfter completion of the reaction
10. customthe reaction mixture was quenched with 30% aqueous potassium carbonate (5.5 ml)
11. filtrationthe solid precipitate was filtered
12. concentrationpartially concentrated
13. additiontoluene (100 ml) added
14. washby washed with 30% citric acid solution in water (50 ml)
15. concentrationThe organic layer was partially concentrated
16. additionhexane (50 ml) was added
17. temperatureThe mixture was cooled to 0° C.
18. filtrationfiltered
19. washthe solid precipitate was washed with chilled hexane (10 ml)
20. customThe wet product was dried at 50° C. to 55° C. under reduced pressure