Sodium Carbonate → (2E)-3-[5-(Cyclopropylcarbamoyl)-4-(trifluoromethyl)pyridin-2-yl]acrylic acid

Temperature

120 °C

N-Cyclopropyl-6-iodo-4-(trifluoromethyl)nicotinamide (125 mg, 0.34 mmol) and ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (93 mg, 0.41 mmol) were dissolved in 2 ml of 1,4-dioxane and admixed under argon with sodium carbonate (180 mg, 1.72 mmol) and bis(tricyclohexylphosphine)palladium(II) dichloride. The reaction mixture was heated in a microwave (CEM Discover) at 120° C. (80 W) for 10 min. Then the reaction mixture was filtered through kieselguhr, and the filtrate was taken up in ethyl acetate, washed with hydrochloric acid (1 M), dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue was taken up in 1.5 ml of ethanol, admixed with sodium hydroxide solution (1M) and stirred at room temperature overnight. Then the reaction mixture was added to ice-cold dilute hydrochloric acid and extracted with ethyl acetate. The organic phase was dried over sodium sulphate, filtered and concentrated to dryness under reduced pressure.

1. filtrationThen the reaction mixture was filtered through kieselguhr
2. washwashed with hydrochloric acid (1 M)
3. dry with materialdried over magnesium sulphate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. additionThen the reaction mixture was added to ice-cold dilute hydrochloric acid
7. extractionextracted with ethyl acetate
8. dry with materialThe organic phase was dried over sodium sulphate
9. filtrationfiltered
10. concentrationconcentrated to dryness under reduced pressure

ORD record

ord-7c87c2bad9694334b31ebb1d4717b157

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08710242B2