Patent ID: 7074931

Claim:
A process for making a 1,4-dihydropyridine, said process comprising: a) forming a substituted or unsubstituted substantially homo-chiral vinylogous amide by: (i) dissolving a substituted or unsubstituted cyclohexanone and a substituted or unsubstituted substantially homo-chiral phenylethylamine in acetonitrile; (ii) refluxing to remove water so as to form said vinylogous amide, and (iii) isolating said vinylogous amide by evaporating volatile materials; b) forming a substituted or unsubstituted Î±,Î²-unsaturated ketone by: (iv) reacting an aldehyde with a amine-reagent selected from pyrrolidine, piperidine, morpholine and diethylaminepyrrolidine in dichloromethane at a temperature of 0â€“10Â° C. to form an intermediate, and (v) reacting said intermediate with a substituted or unsubstituted ketone by adding trifluoroacetic acid while maintaining a temperature at 0â€“10Â° C., to form said Î±,Î²-unsaturated ketone; c) dissolving said vinylogous amide in acetonitrile inerted under nitrogen at a temperature about 25Â° 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 25â€“40 minutes while maintaining said temperature at about 25Â° C. to form a reaction mixture and maintaining said temperature at about 25Â° C. for about 30 minutes; e) cooling said reaction mixture to a temperature about 4â€“10Â° C. and adding said Î±,Î²-unsaturated ketone dissolved in acetonitrile inerted under nitrogen over 25â€“40 minutes while maintaining said temperature; f) maintaining said reaction mixture at 5Â° C. for 5â€“10 hours, then heating to and maintaining at 24â€“28Â° C. for 17â€“24 hours and further heating to and maintaining at 40â€“45Â° C. for 6â€“10 hours; g) cooling said reaction mixture to 8â€“15Â° C. and adding ammonia over 30â€“60 minutes; h) heating said reaction mixture to 50â€“90Â° 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, AMBERLYSTâ„¢ 15 (ion exchange resin), and concentrated hydrochloric acid over 25â€“40 minutes while maintaining a temperature of 10â€“25Â° C. followed by heating to reflux to form a 1,4-dihydropyridine.