Diphenyl Ether → Ethyl 2,4-dihydroxy-6-methylpyridine-3-carboxylate

Temperatur

160 °C

In a 22 L vessel fitted with a mechanical stirrer and distillation head was charged 2.5 L (16.47 mol) diethyl malonate followed by 4.0 L diphenyl ether. Agitation was started and 1.12 Kg (16.47 mol, 1 eq) of sodium ethoxide was added via a powder funnel. The mixture was gradually, heated to 160° C. and the liberated ethanol was removed via distillation, approximately 950 mL. After 30 min, ethanol distillation ceased and 2.127 Kg (16.47 mol, 1 eq) of 3-amino-but-2-enoic acid ethyl ester was added, and the resulting ethanol formed removed via distillation. After 30 minutes the mechanical stirrer could no longer stir the foamy mass. At this point, external heating was ceased and the mixture allowed to cool to ambient temperature. To the mixture was charged 4 L of methyl-tert-butyl ether (MTBE) and the granular solid broken up with a spatula. The solid was filtered and washed with MTBE. To the solid was then added 100 mL of conc. HCl and 2 L of chloroform to solublize the mixture. The mixture was then taken up three times in 4 L chloroform, and decanted into a 20 L bucket. The combined organic phases were dried over sodium sulfate. The mixture was concentrated in vacuo to afford an orange gummy mass, which was triturated with MTBE and filtered, washing the filter cake with MTBE. The resulting solid was recrystallized from ethanol to afford the desired product as pinkish needles.

1. customIn a 22 L vessel fitted with a mechanical stirrer
2. distillationdistillation head
3. customthe liberated ethanol was removed via distillation, approximately 950 mL
4. distillationethanol distillation
5. customremoved via distillation
6. temperatureAt this point, external heating
7. temperatureto cool to ambient temperature
8. additionTo the mixture was charged 4 L of methyl-tert-butyl ether (MTBE)
9. filtrationThe solid was filtered
10. washwashed with MTBE
11. additionTo the solid was then added 100 mL of conc. HCl and 2 L of chloroform
12. customdecanted into a 20 L bucket
13. dry with materialThe combined organic phases were dried over sodium sulfate
14. concentrationThe mixture was concentrated in vacuo
15. customto afford an orange gummy mass, which
16. customwas triturated with MTBE
17. filtrationfiltered
18. washwashing the filter cake with MTBE
19. customThe resulting solid was recrystallized from ethanol

ORD-Eintrag

ord-586e24b10a224a5492bd89047e7ac4cd

Quelldatensatz

uspto-grants-2007_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07273871B2