Carbon Dioxide → Methyl 2-{2-hydroxy-1-[(methyloxy)carbonyl]ethenyl}-1-methyl-1H-pyrrole-3-carboxylate

Temperatur

118 °C

To a suspension of methyl 1-methyl-2-[2-(methyloxy)-2-oxoethyl]-1H-pyrrole-3-carboxylate (37.9 g) in THF (anhydrous, 300 ml), under argon, was added sodium hydride (60% dispersion in mineral oil, 37.9 g) portion-wise. After complete addition the reaction was stirred at 22° C. for 15 minutes before the drop-wise addition of methyl formate (16.6 ml). The reaction was stirred at 118° C. for 50 minutes. During this period the temperature increased to around 21.5° C. before a rapid rise in temperature with gas evolution. Cooling (solid carbon dioxide) was applied to the outside of the flask. The temperature reached a maximum of 30° C. before dropping to 20° C. The coolant was removed and the reaction stirred for a further 17 hours. The reaction mixture was cooled by an ice/water bath before the cautious addition of methanol (100 ml). The reaction mixture was then combined with the product of another second mixture prepared in a similar manner (starting weight of methyl 1-methyl-2-[2-(methyloxy)-2-oxoethyl]-1H-pyrrole-3-carboxylate was 35.5 g). The solution was concentrated in vacuo. The residue was treated with saturated ammonium chloride solution (600 ml) then acidified to pH1 by the cautious addition concentrated hydrochloric acid. Ice was added to cool the solution and it was then extracted with ethyl acetate (3×400 ml). The combined organics were dried (MgSO4) and the solvent removed to yield a black oily solid. Oil was decanted and the residue triturated with hexane (2×200 ml), diethyl ether (200 ml) and hexane (200 ml). This yielded the title compound as a brown solid (65.2 g).

1. additionAfter complete addition the reaction
2. temperatureDuring this period the temperature increased to around 21.5° C. before a rapid rise in temperature with gas evolution
3. customa maximum of 30° C.
4. custombefore dropping to 20° C
5. customThe coolant was removed
6. stirringthe reaction stirred for a further 17 hours
7. temperatureThe reaction mixture was cooled by an ice/water bath before the cautious addition of methanol (100 ml)
8. customprepared in a similar manner (starting weight of methyl 1-methyl-2-[2-(methyloxy)-2-oxoethyl]-1H-pyrrole-3-carboxylate was 35.5 g)
9. concentrationThe solution was concentrated in vacuo
10. additionThe residue was treated with saturated ammonium chloride solution (600 ml)
11. additionthen acidified to pH1 by the cautious addition concentrated hydrochloric acid
12. additionIce was added
13. temperatureto cool the solution and it
14. extractionwas then extracted with ethyl acetate (3×400 ml)
15. dry with materialThe combined organics were dried (MgSO4)
16. customthe solvent removed
17. customto yield a black oily solid
18. customOil was decanted
19. customthe residue triturated with hexane (2×200 ml), diethyl ether (200 ml) and hexane (200 ml)

ORD-Eintrag

ord-d5092b86ffa64a14b832813fb7bbd908

Quelldatensatz

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07589206B2