Patent ID: 7074931
Filing Date: 2006-07-11
Classification: C07D

Abstract:
1. A process for making a 1,4-dihydropyridine, said process comprising: a) forming a substituted or unsubstituted substantially homo-chiral vinylogous amide by: b) forming a substituted or unsubstituted α,β-unsaturated ketone by: c) dissolving said vinylogous amide in acetonitrile inerted under nitrogen at a temperature about 25° C.; d) adding to the amide of step c) a silicon reagent selected from: trimethylsilyl chloride, triethylsilyl chloride, triphenylsilyl chloride, trimethylsilyltriflate and tributylsilyl chloride over 25–40 minutes while maintaining said temperature at about 25° C. to form a reaction mixture and maintaining said temperature at about 25° C. for about 30 minutes; e) cooling said reaction mixture to a temperature about 4–10° C. and adding said α,β-unsaturated ketone dissolved in acetonitrile inerted under nitrogen over 25–40 minutes while maintaining said temperature; f) maintaining said reaction mixture at 5° C. for 5–10 hours, then heating to and maintaining at 24–28° C. for 17–24 hours and further heating to and maintaining at 40–45° C. for 6–10 hours; g) cooling said reaction mixture to 8–15° C. and adding ammonia over 30–60 minutes; h) heating said reaction mixture to 50–90° C. for about 17 hours in a pressure vessel; i) recovering the acetonitrile phase and adding an acid selected from: methane-sulfonic acid, trifluoroacetic acid, acetic acid, para-toluene sulfonic acid, AMBERLYST™ 15 (ion exchange resin), and concentrated hydrochloric acid over 25–40 minutes while maintaining a temperature of 10–25° C. followed by heating to reflux to form a 1,4-dihydropyridine.