Potassium Carbonate → 3-(5-(Tert-butyl)-2-((2-methoxyethoxy)methoxy)phenyl)-6-(trifluoromethyl)pyridazine

Temperatur

80 °C

A mixture of 3-chloro-6-trifluoromethylpyridazine [purchased from Combi-Blocks] (250 mg, 1.37 mmol), (5-(tert-butyl)-2-((2-methoxyethoxy)methoxy)phenyl)boronic acid [Intermediate 7] (463.8 mg, 1.64 mmol) and potassium carbonate (284.5 mg, 2.06 mmol) in dimethoxyethane (7.5 mL) and water (2.5 mL) was purged with nitrogen for 20 minutes. Tetrakis(triphenylphosphine)palladium(0) (79.1 mg, 0.068 mmol) was added and the reaction mixture heated to 80° C. in a sealed vial for 22 hours. The cooled reaction mixture was partitioned between ethyl acetate (50 mL) and 10% aqueous sodium carbonate solution (50 mL), the organic phase separated, washed with water (50 mL) and saturated brine (50 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give a brown syrup. The crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 30% ethyl acetate in hexanes to give 3-(5-(tert-butyl)-2-((2-methoxyethoxy)methoxy)phenyl)-6-(trifluoromethyl)pyridazine (0.462 g, 88% yield) as a colorless syrup.

1. customwas purged with nitrogen for 20 minutes
2. customThe cooled reaction mixture
3. customwas partitioned between ethyl acetate (50 mL) and 10% aqueous sodium carbonate solution (50 mL)
4. customthe organic phase separated
5. washwashed with water (50 mL) and saturated brine (50 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto give a brown syrup
10. customThe crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 30% ethyl acetate in hexanes

ORD-Eintrag

ord-51d378642bdf4ee0b455b53f6ff3cf78

Quelldatensatz

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09409893B2