Cesium carbonate → 5-Cyclopropyl-6-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid

Temperatur

120 °C

In a 150 ml round-bottom-flask, Pd(OAc)2 (15.7 mg, 70.0 μmol), butyl-1-adamantylphosphin (37.6 mg, 105 μmol), potassium cyclopropyltrifluoroborate (523 mg, 3.53 mmol), cesium carbonate (3.42 g, 10.5 mmol) and 5-bromo-6-(2,2,2-trifluoroethoxy)picolinic acid (Example 282a) (1.05 g, 3.5 mmol) were combined. The flask was evacuated in vacuo and flushed with argon three times, followed by addition of a mixture toluene (25 ml)/H2O (3 ml) through a septum cap. The reaction mixture was heated to 120° C., stirred for 20 h and then cooled to ambient temperature. Evaporation of volatiles in vacuo and the residue was redissolved in ethyl acetate and extracted with 1M HCl (12.5 ml). The aqueous phase was back-extracted with ethyl acetate. The combined organic layers were dried over Na2SO4 and concentrated in vacuo The crude material was purified by flash chromatography (silica gel, 50 g, 0% to 5% MeOH in DCM) to give the title compound (530 mg, 58%). MS (EI): m/e=262.2[M+H]+.

1. customThe flask was evacuated in vacuo
2. customflushed with argon three times
3. additionfollowed by addition of a mixture toluene (25 ml)/H2O (3 ml) through a septum
4. customcap
5. temperaturecooled to ambient temperature
6. customEvaporation of volatiles in vacuo
7. dissolutionthe residue was redissolved in ethyl acetate
8. extractionextracted with 1M HCl (12.5 ml)
9. extractionThe aqueous phase was back-extracted with ethyl acetate
10. dry with materialThe combined organic layers were dried over Na2SO4
11. concentrationconcentrated in vacuo The crude material
12. customwas purified by flash chromatography (silica gel, 50 g, 0% to 5% MeOH in DCM)

ORD-Eintrag

ord-c626cdfda4ca4fea95035200c0666d64

Quelldatensatz

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09321727B2