Reaktion #342581

Reaktionsgleichung

ethyl trifluoroacetate

BuLi

ethyl 2-acetyl-3-amino-4,4,4-trifluoro-2-butenoate

Ethyl 2-acetyl-3-amino-4,4,4-trifluoro-2-butenoate

HCl

diisopropylamine

→

Ethyl 2,6-bis(trifluoromethyl)-4-hydroxy-3-pyridinecarboxylate

Lösungsmittel

hexane

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeTo a flame dried
2. 2
   Sonstige3-liter, four-necked flask equipped with nitrogen inlet
3. 3
   workup.ADDITIONlow temperature thermometer, 500 ml addition funnel and mechanical stirrer
4. 4
   Sonstigewas kept below -60° C
5. 5
   Sonstigewas kept below -60° C
6. 6
   Sonstigea solid suspension formed
7. 7
   workup.STIRRINGAfter 1 hour of stirring at -78° C.
8. 8
   Sonstigewas kept below -60° C
9. 9
   workup.WAITThis reaction mixture was left at -78° C for 1 hour
10. 10
    Temperaturwarmed to room temperature (the yellow suspension
11. 11
    Sonstigea brown solution was formed) and
12. 12
    workup.STIRRINGstirred for 18 hours
13. 13
    Extraktionextracted 3 times with methylene chloride
14. 14
    TrocknenThe combined methylene chloride layers were dried (MgSO° )
15. 15
    Sonstigeaffording a brown thick oil
16. 16
    workup.DISTILLATIONThe residue was kugelrohr distilled at 47 Pa
17. 17
    SonstigeThe earlier fraction (pot temperature 50° C.)
18. 18
    SonstigeThe later fraction (pot temperature 80° C.) afforded 80.0 g (66) of the pyridine product, mp 70°-77° C

Vorschrift

To a flame dried, 3-liter, four-necked flask equipped with nitrogen inlet, low temperature thermometer, 500 ml addition funnel and mechanical stirrer was charged 91.0 g (126 ml, 0.899 mol) of diisopropylamine and 500 ml of dry tetrahydrofuran. The resulting solution was cooled to -78° C. using an acetone-dry ice bath. To this was slowly added 383 ml (0.880 mol) of 2.3M -BuLi in hexane at such a rate that the reaction temperature was kept below -60° C. After stirring at -78° C. for 1 hour, a solution of 90.0 g (0.400 mol) of ethyl 2-acetyl-3-amino-4,4,4-trifluoro-2-butenoate from Example 1 in 150 ml of dry tetrahydrofuran was added at such a rate that the reaction temperature was kept below -60° C. The reaction mixture turned yellow and a solid suspension formed. After 1 hour of stirring at -78° C., the reaction mixture was treated with 184.7 g (155 ml, 1.300 mol) of ethyl trifluoroacetate at such a rate that the reaction temperature was kept below -60° C. This reaction mixture was left at -78° C for 1 hour, then warmed to room temperature (the yellow suspension disappeared and a brown solution was formed) and stirred for 18 hours. The resulting solution was poured into 1.5 L of 10% HCl (aq.) and extracted 3 times with methylene chloride. The combined methylene chloride layers were dried (MgSO° ) and reduced in vacuo affording a brown thick oil. The residue was kugelrohr distilled at 47 Pa. The earlier fraction (pot temperature 50° C.) was discarded. The later fraction (pot temperature 80° C.) afforded 80.0 g (66) of the pyridine product, mp 70°-77° C. Anal. Calc'd. for C10H7F6N1O3 : C, 39.62; H, 2.33;

Quelle