Malonic Acid → 3',4'-Dimethoxycinnamic acid

To a solution of 1000 g (6.024 mol) of 3,4-dimethoxybenzaldehyde in 3 L pyridine, 1378.3 g (13.25 mol) of malonic acid and 100 mL of piperidine were added. The resulting mixture was stirred at 105° C. to 110° C. for 6-8 h. After completion of the reaction, the reaction mixture was cooled to 25° C. to 30° C. and slowly quenched the reaction mixture into 10 L of 5% sodium hydroxide solution at 25° C. to 30° C. (pH: 9-10). The reaction mixture was washed with ethyl acetate (2×5 L) and the organic layer separated was washed with 2 L of 5% sodium hydroxide solution. The aqueous layers were combined and cooled to 15° C. to 20° C. The aqueous layer was acidified slowly with 2.5 L of 50% sulphuric acid below 20° C. (pH: 1-2). After an additional 30-45 min stirring at 15° C. to 20° C., the solid obtained was collected by filtration, washed with 10 L of water followed by 4 L of n-hexane. The partially dried compound was unloaded into trays and dried at 55° C. to 60° C. for 8-10 h to give 1110 g of the title compound.

1. customAfter completion of the reaction
2. temperaturethe reaction mixture was cooled to 25° C. to 30° C.
3. customslowly quenched the reaction mixture into 10 L of 5% sodium hydroxide solution at 25° C. to 30° C. (pH: 9-10)
4. washThe reaction mixture was washed with ethyl acetate (2×5 L)
5. customthe organic layer separated
6. washwas washed with 2 L of 5% sodium hydroxide solution
7. temperaturecooled to 15° C. to 20° C
8. customwas acidified slowly with 2.5 L of 50% sulphuric acid below 20° C. (pH: 1-2)
9. stirringAfter an additional 30-45 min stirring at 15° C. to 20° C.
10. customthe solid obtained
11. filtrationwas collected by filtration
12. washwashed with 10 L of water
13. customdried at 55° C. to 60° C. for 8-10 h

ORD record

ord-19ad2197df304b3c9b510e76b8e6b50b

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08629277B2