Hydrochloric Acid → HCID 178470034, compound

Temperature

-78 °C

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 n-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 (MgSO4) 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.

1. customTo a flame dried
2. custom3-liter, four-necked flask equipped with nitrogen inlet
3. additionlow temperature thermometer, 500 ml addition funnel and mechanical stirrer
4. customwas kept below -60° C
5. customwas kept below -60° C
6. customa solid suspension formed
7. stirringAfter 1 hour of stirring at -78° C.
8. customwas kept below -60° C
9. waitThis reaction mixture was left at -78° C. for 1 hour
10. temperaturewarmed to room temperature (the yellow suspension
11. customa brown solution was formed) and
12. stirringstirred for 18 hours
13. extractionextracted 3 times with methylene chloride
14. dry with materialThe combined methylene chloride layers were dried (MgSO4)
15. customaffording a brown thick oil
16. distillationThe residue was kugelrohr distilled at 47 Pa
17. customThe earlier fraction (pot temperature 50° C.)
18. customThe later fraction (pot temperature 80° C.) afforded 80.0 g (66%) of the pyridine product, mp 70°-77° C.

ORD record

ord-1b57e286b8584871afed6535c9d8ad30

Source dataset

uspto-grants-1990_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04921530