General method: 4-(4-Chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester and methyl acetoacetate were used to synthesize 4-(4-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester. First, methyl acetoacetate (1.34 M) was mixed with 25% aqueous NH3 solution (3 mL), and then this mixture was loaded into gas-tight syringe 1 and syringe 2 with an EtOH solution (3 mL) of diethyl 4-(4-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (0.67 M), respectively. The syringes were mounted on a LongerLSP02-1B syringe pump and the flow rate was set to 6.7 μL/min to ensure that both reactants entered the mixer at the same flow rate. The mixed reactants flowed through a stainless steel tube reactor immersed in a 110°C oil bath. Upon completion of the reaction, the output mixture was collected in a cooled sample bottle. The reactor was thoroughly rinsed with ethanol and all reaction solutions were combined and subsequently concentrated under vacuum. The resulting residue was purified by silica gel column chromatography using petroleum ether-ethyl acetate (5:1) as eluent to give the final target product dimethyl 4-(4-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (612 mg, 93% yield).
