103890-78-4

59159-39-6

626-34-6

643-79-8

103890-78-4

1. 18 liters of dichloromethane were added to the reactor, followed by 5 kg of tert-butoxycarbonylmethyltriphenylphosphonium bromide (prepared with reference to Example 1). 2. 2.05 kg of o-phthalaldehyde was added, followed by 1 liter of dichloromethane, and the mixture was stirred for about 15 minutes, then cooled to -5°C. 3. A solution of 2.65 kg of sodium hydroxide flakes in 5 liters of water (pre-prepared at 25°C) was added to the reaction mixture at -3°C and kept at -3°C for 2.5 hours. The reaction process was monitored by thin layer chromatography. 4. After completion of the reaction, the mixture was warmed up to 25°C and stirring was continued for 30 minutes. The organic layer was separated and the solvent was removed by atmospheric pressure distillation at 52°C. The residue was kept at 52°C for 15 minutes. 5. 35 liters of n-heptane were added and 4 liters of n-heptane were distilled under 500 mmHg vacuum and at 63 °C. The mixture was then cooled to 0°C and held at 35°C for 1.5 hours. 6. The insoluble material was removed by vacuum filtration and the filter cake was washed with 7.5 liters of n-heptane. The filtrate was transferred to another reactor and the solvent was removed by complete distillation under vacuum at 610 mmHg and 68°C. 7. Cooled to 33 °C, 11.5 liters of isopropanol was added and subsequently cooled to -7 °C. 8. At -7 °C, a solution of 4.25 kg ethyl 3-aminocrotonate in 12.5 liters of isopropanol was slowly added, followed by 2.8 liters of trifluoroacetic acid and 1 liter of isopropanol, and the reaction was kept at -7 °C for 2 hours and 45 minutes. The reaction process was monitored by thin layer chromatography. 9. A solution of 2.6 kg of sodium bicarbonate in 50 liters of water was added to the reaction mixture at 0 °C, followed by 25 liters of ethyl acetate. Increase the temperature to 25°C and stir for 20 minutes. Separate the aqueous layer and extract with 12.5 liters of ethyl acetate. The organic layers were combined and the solvent was removed by atmospheric pressure distillation at 81 °C. 10. Add 5 liters of isopropanol to the residue and distill completely to remove the solvent. This operation is repeated once. Finally, the residue was dissolved in 63 liters of isopropanol and heated to 85°C to obtain a clarified solution. 11. Cool to 2 °C, keep for 1.5 h. Separate the solid by filtration and wash with 2.5 liters of isopropanol. The wet product was dried at 50°C for 30 minutes. 12. The dried substance was added to 23 liters of isopropanol, heated to 65°C and held for 30 minutes, cooled to 2°C and held for 1 hour, filtered and washed with 1.5 liters of isopropanol. 13. The wet solid was dried at 60 °C and 630 mmHg under vacuum for 5 h to give 2.04 kg of ethyl (E)-diethyl 4-(2-(3-(tert-butoxy)-3-oxoprop-1-en-1-yl)phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate in 40.9% yield. The content of triphenylphosphine oxide was less than 0.0011 area%.