Potassium Carbonate → 1-(5-Chloro-2-hydroxy-4-methyl-3-pyridin-4-ylphenyl)ethanone

Temperature

90 °C

A solution of 1-(3-bromo-5-chloro-2-hydroxy-4-methylphenyl)ethanone (2.6 g, 9.9 mmol), 4-pyridinylboronic acid (1.6 g, 13 mmol), and potassium carbonate (5.5 g, 40 mmol) in 1,2-dimethoxyethane (48 mL) and water (24 mL) was degassed with nitrogen and treated with triphenylphosphine (260 mg, 0.99 mmol) and palladium acetate (0.22 g, 0.99 mmol). The reaction mixture was degassed with nitrogen for 5 min and heated at 90° C. for 20 hours. The reaction mixture was cooled to room temperature, concentrated to remove most of the DME, diluted with ethyl acetate (200 ml) and water (100 ml), and filtered over celite. The aqueous layer was separated and extracted with ethyl acetate (100 mL). The combined organic layers were washed with brine (100 ml), dried over sodium sulfate, filtered, and concentrated to a crude brown foam. Purification by flash column chromatography using ethyl acetate in hexanes (0%-60%) gave the desired product (1.2 g, 45%). LCMS for C14H13ClNO2 (M+H)+: m/z=262.1. Found: 262.0.

1. customThe reaction mixture was degassed with nitrogen for 5 min
2. temperatureThe reaction mixture was cooled to room temperature
3. concentrationconcentrated
4. customto remove most of the DME
5. additiondiluted with ethyl acetate (200 ml) and water (100 ml)
6. filtrationfiltered over celite
7. customThe aqueous layer was separated
8. extractionextracted with ethyl acetate (100 mL)
9. washThe combined organic layers were washed with brine (100 ml)
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated to a crude brown foam
13. customPurification by flash column chromatography

ORD record

ord-4d625b22401d4f1b83dd4be9f98d9df5

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096600B2