| production method | The acrylate and isopropylamine were stirred at room temperature in the presence of a salt catalyst, and then slowly increased to a temperature of 100-110 °c. Methyl acrylate was distilled off under reduced pressure, and a fraction of 131 to 135 ° C./1.47kPa was collected to obtain N,N bis (2-methoxycarbonylethyl) isopropylamine in a yield of 83.5. It was stirred with solid sodium methoxide and anhydrous toluene at 100-105 °c. The fraction below 80 ° C. Was distilled off, anhydrous toluene was added, and the mixture was refluxed. After cooling, glacial acetic acid and water were added, the toluene layer was separated, and the aqueous layer was extracted with toluene. The toluene layer was extracted with concentrated hydrochloric acid, and all the acids were combined and decarboxylated at 110 °c. After treatment, n-isopropyl-4-piperidone was obtained in a yield of 33%. The piperidone, P-chloroaniline, P-toluenesulfonic acid and toluene were refluxed to separate water. The 178-180 °c/1.47kPa fraction was collected to give 1-isopropyl-4-(p-chlorophenylimino) piperidine in a yield of 83%. The piperidine was dissolved in methanol, and potassium borohydride was added in portions to give a chloroform solution of 1-isopropyl-4-(p-chlorophenylamino) piperidine; The chloroform solution and phenylacetyl chloride were refluxed, hydrochloric acid was acidified to Ph = 3. The crude product was recrystallized from a mixed solvent of isopropanol and acetone to obtain lorcainide. The yield of the two steps was 63.6, and the melting point was 263~265 ℃. |
