2,2,2-Trifluoroethanol → Efavirenz aminoalcohol

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

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.

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