METHODS OF PREPARING 1-(4-((1R,2S,3R)-1,2,3,4-TETRAHYDROXYBUTYL)-1H-IMIDAZOL-2-YL)ETHANONE
Methods of preparing 1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone and derivatives thereof are disclosed.
1 . A method of preparing 1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone, which comprises:
contacting 2-ethoxyacrylimidate with a weak acid salt of D-glucosamine to provide a first mixture;
contacting the first mixture with a base to provide a second mixture;
adding an aqueous acid to the second mixture to provide a third mixture;
maintaining the third mixture at a temperature of greater than 30° C. for at least 0.5 hours; and
isolating 1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone from the third mixture.
2 . The method of claim 1 , wherein the weak acid salt of D-glucosamine is D-glucosamine acetate.
3 . The method of claim 2 , wherein the base is an alkaline or alkaline earth metal alkoxide, hydroxide, carbonate, phosphate, or trialkylamine.
4 . The method of claim 3 , wherein the base is methoxide.
5 . The method of claim 1 , wherein the first mixture is maintained at a temperature of greater than 10° C. for at least 0.5 hours.
6 . The method of claim 1 , wherein the second mixture is maintained at a temperature of greater than 5° C. for at least 1 hour.
7 . The method of claim 1 , wherein the third mixture is maintained at a temperature of greater than 50° C., for at least 0.5 hours.
8 . The method of claim 1 , wherein the aqueous acid has a pK a of from 0 to 10.
9 . The method of claim 8 , wherein the aqueous acid is formic, acetic, or trichloroacetic acid.
10 . The method of claim 9 , wherein the aqueous acid is acetic acid.
11 . The method of claim 1 , wherein the 1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone is isolated by filtering a slurry prepared by concentrating, cooling and/or diluting the third mixture with water.
12 . (canceled)
13 . The method of claim 1 , wherein the 2-ethoxyacrylimidate is prepared by contacting 2-ethoxyacrylonitrile with an alcohol and an alkaline or alkaline earth metal alkoxide to provide a fourth mixture.
14 . The method of claim 13 , wherein the fourth mixture is maintained at a temperature of greater than 0° C. for at least 2 hours.
15 . 1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone prepared by the method of claim 1 .