Dichloromethane → HCID 136408092, compound

Temperature

85 °C

To a nitrogen de-gassed mixture of 3-bromo-5-(tert-butyl)-2-hydroxybenzaldehyde [CAS #119646-68-3] (1.00 g, 3.89 mmol), bis(pinacolato)diboron (1.98 g, 7.80 mmol), and potassium acetate (1.15 g, 11.7 mmol) in dioxane (50 mL) under a nitrogen was added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (285 mg, 0.39 mmol) and the reaction mixture heated to 85° C. for 16 hours. The reaction was allowed to cool to 25° C. at which time 2M aqueous sodium carbonate (9.7 mL, 19.5 mmol) and 2-chloro-4-trifluoromethylpyrimidine (1.42 g, 7.78 mmol) were added and the solution degassed with nitrogen. A second portion of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (285 mg, 0.39 mmol) was added and the mixture heated at 85° C. under a nitrogen atmosphere for 6 hours. The cooled reaction mixture was then partitioned between ethyl acetate (100 mL) and a saturated aqueous solution of sodium bicarbonate (100 mL). The organic phase was separated, concentrated under reduced pressure and purified using flash chromatography on silica eluting with a solvent gradient of 0 to 70% ethyl acetate in hexanes to give 5-(tert-butyl)-2-hydroxy-3-(4-(trifluoromethyl)pyrimidin-2-yl)benzaldehyde (350 mg, 28% yield) as a cream solid.

1. customTo a nitrogen de-gassed
2. additionwere added
3. customthe solution degassed with nitrogen
4. temperaturethe mixture heated at 85° C. under a nitrogen atmosphere for 6 hours
5. customThe cooled reaction mixture
6. customwas then partitioned between ethyl acetate (100 mL)
7. customThe organic phase was separated
8. concentrationconcentrated under reduced pressure
9. custompurified

ORD record

ord-5b1b6571b7954221b39a0808904f0735

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09409893B2