Efficient process to induce enantioselectivity in procarbonyl compounds
View Patent ↗An efficient method to induce the enantioselectivity in procarbonyl compounds using chiral organometallic complexes. The present invention is also described a method for producing organo metallic complexes using a base and a metal halide.
1. A process for the preparation of an amino alcohol of formula:
wherein
R 1 is amino;
R 2 is cyclopropylethynyl;
the process comprising the steps of:
slowly adding 2,2,2-trifluoroethanol and achiral additive to a base to form a reaction mass, wherein the chiral additive is selected from the group consisting of (1R,2S)-pyrrolidinyl norephidrine, its enantiomers, and diastereomers, and wherein the base is selected from the group consisting of metal hydrides, metal alkoxides and metal hydroxides in an organic solvent;
treating the reaction mass with a metal halide to obtain a chiral metal complex, wherein the metal halide is selected from the group consisting of zinc halide and copper halide;
adding an organometallic reagent of formula R 2 M to the chiral metal complex in a solvent to form a suspension, wherein M is Li or MgX, and X is a halo;
stirring the suspension to obtain a chiral organometal complex; and
mixing 4-chloro-2-trifluoroacetylaniline with the chiral organometal complex to produce the desired chiral amino alcohol.
2. The process of claim 1 , wherein the metal hydride is sodium hydride.
3. The process of claim 1 , wherein the metal halide is zinc chloride or zinc bromide.
4. The process of claim 1 , wherein the organometallic reagent cyclopropylacetylide magnesium chloride.