Acrolein → Ethyl 2-methylnicotinate

Temperature

100 °C

To a mixture of 800 ml. of ethyl 3-aminocrotonate, 30 ml. of piperidine and 1.4 l. of isopropanol, stirred at 25°-30° C., 540 ml. of acrolein were added slowly over a 2 hour period with stirring. Upon completion of the addition of the acrolein, the reaction mixture was heated to reflux and refluxed for 31/2 hours. Then the reaction mixture was evaporated at reduced pressure to dryness. The residue was heated to 100° C. and 610 g. of sulfur were added thereto portionwise. The reaction mixture was then heated at 100° C. for 2 hours and at 125° C. for 11/2 hours. The reaction mixture was allowed to cool to about room temperature and 1 l. of chloroform was added thereto. The reaction mixture was filtered through Celite and the filter cake was washed with additional chloroform. The combined chloroform filtrate and washings were extracted three times with 1 l. portions of 2 N. hydrochloric acid. The aqueous acidic layers were combined and, with cooling, were made basic with 2 N. sodium hydroxide solution. The obtained aqueous basic solution was extracted three times with 1 l. portions of chloroform. The chloroform extracts were combined, washed with saturated brine, dried over anhydrous sodium sulfate and evaporated at reduced pressure to obtain an oily residue which was distilled under high vacuum to obtain the pure product (350 g.), b.p. 73°-77° C./0.5 mm. Hg.

1. additionTo a mixture of 800 ml
2. temperaturethe reaction mixture was heated
3. temperatureto reflux
4. temperaturerefluxed for 31/2 hours
5. customThen the reaction mixture was evaporated at reduced pressure to dryness
6. additionof sulfur were added
7. temperatureThe reaction mixture was then heated at 100° C. for 2 hours and at 125° C. for 11/2 hours
8. temperatureto cool to about room temperature
9. additionof chloroform was added
10. filtrationThe reaction mixture was filtered through Celite
11. washthe filter cake was washed with additional chloroform
12. extractionThe combined chloroform filtrate and washings were extracted three times with 1 l
13. temperaturewith cooling
14. extractionThe obtained aqueous basic solution was extracted three times with 1 l
15. washwashed with saturated brine
16. dry with materialdried over anhydrous sodium sulfate
17. customevaporated at reduced pressure
18. customto obtain an oily residue which
19. distillationwas distilled under high vacuum
20. customto obtain the pure product (350 g.), b.p. 73°-77° C./0.5 mm. Hg

ORD record

ord-6b7498a3e458407d8748911a44214c20

Source dataset

uspto-grants-1982_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04329349