Potassium Acetate → 1-cyclobutyl-5-fluoro-6-hydroxy-1H-indole-3-carbonitrile

Temperature

80 °C

A mixture of 6-bromo-1-cyclobutyl-5-fluoro-1H-indole-3-carbonitrile (29.9 g, 102 mmol), bis(pinacolato)diboron (33.7 g, 133 mmol), PdCl2dppf-CH2Cl2 complex (4.16 g, 5.1 mmol) and potassium acetate (30 g, 306 mmol) in dioxane (300 mL) was stirred at 80° C. overnight. The mixture was then cooled to room temperature, treated with ethyl acetate (200 mL) and filtered through a silica-celite pad. The filtrate was concentrated, dissolved in acetone (300 mL) and cooled to 0° C. Into this solution was added a slurry of Oxone (125.5 g, 204 mmol) in water (300 mL). The mixture was stirred at room temperature for 15 min, diluted with ethyl acetate and separated. The aqueous layer was extracted with ethyl acetate. The organic extractions were combined and washed with sat. aq. NaHSO3, and brine, dried over Na2SO4 and concentrated. The residue was purified on silica gel to provide 1-cyclobutyl-5-fluoro-6-hydroxy-1H-indole-3-carbonitrile as a light grey solid (19.2 g, 82%).

1. temperatureThe mixture was then cooled to room temperature
2. filtrationfiltered through a silica-celite pad
3. concentrationThe filtrate was concentrated
4. dissolutiondissolved in acetone (300 mL)
5. temperaturecooled to 0° C
6. stirringThe mixture was stirred at room temperature for 15 min
7. customseparated
8. extractionThe aqueous layer was extracted with ethyl acetate
9. extractionThe organic extractions
10. washwashed with sat. aq. NaHSO3, and brine
11. dry with materialdried over Na2SO4
12. concentrationconcentrated
13. customThe residue was purified on silica gel

ORD record

ord-9d0c8ffecc2b46f9b63403ee9c36d05b

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08735414B2