2-Methylnicotinic acid → HCID 178517527, Verbindung

Temperatur

0 °C

300 mg 2-methyl-nicotinic acid was suspended in 10 mL of tetrahydrofuran, and cooled to −70° C. with a bath of ethanol/dry ice. 3.3 mL lithium diisopropylamide (2.0 M in tetrahydrofuran/n-heptane/ethylbenzene) was added dropwise over 10 min and the mixture was stirred for 1.5 h at 0° C. After this time, it was cooled again to -70° C. and 0.9 g 3-fluoro-4-trifluoromethoxy-benzonitrile (4.1) was added quickly. Then the reaction mixture was stirred for 2 h at −70° C. and then warmed overnight to ambient temperature. The solvent was distilled off, diluted with ethyl acetate, 10 mL phosphate buffer and 5 mL 2N aqueous hydrochloric acid solution (pH 6-7). The formed precipitate was collected and dried. The resulting liquid phase was separated and the water phase extracted twice with ethyl acetate. The organic phase was dried over magnesium sulfate, concentrated and the residue suspended in ether and ethyl acetate. The precipitate was collected, dried and combined with the first precipitate.

1. temperatureAfter this time, it was cooled again to -70° C.
2. stirringThen the reaction mixture was stirred for 2 h at −70° C.
3. temperaturewarmed overnight to ambient temperature
4. distillationThe solvent was distilled off
5. additiondiluted with ethyl acetate, 10 mL phosphate buffer and 5 mL 2N aqueous hydrochloric acid solution (pH 6-7)
6. customThe formed precipitate was collected
7. customdried
8. customThe resulting liquid phase was separated
9. extractionthe water phase extracted twice with ethyl acetate
10. dry with materialThe organic phase was dried over magnesium sulfate
11. concentrationconcentrated
12. customThe precipitate was collected
13. customdried

ORD-Eintrag

ord-fe4f5c4102824377b00db69c21f8a8d2

Quelldatensatz

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08969568B2