Triethylamine → 4-[2-(2-Hydroxyethyl)-1-benzofuran-5-yl]benzonitrile

Temperature

65 °C

To a solution of Example 1A (5.19 g, 16.2 mmol), triethylamine (5.60 mL, 40.4 mmol) and 3-butyn-1-ol (1.90 g, 27.2 mmol) in dimethylformamide (13 mL) at 20° C. was added cuprous iodide (0.46 g, 2.4 mmol) and bis-triphenylphosphine palladium dichloride (0.56 g, 0.80 mmol). The mixture was stirred at 65° C. for 12 hours then cooled to ambient temperature and diluted with dichloromethane (20 mL) and hexane (100 mL). Celite (5 g) was added with stirring and the solids were removed by filtration. The filtrate was washed with water (600 mL). The organic layer was separated and the aqueous layer extracted with dichloromethane (3×100 mL). The combined organic solution was dried (Na2SO4), filtered and concentrated under reduced pressure to give a tan solid. The solid was chromatographed on silica with 3% methanol in dichloromethane to give the titled compound (4.02 g, 95%). MS (DCI) m/z 263 (M+H)+;

1. temperaturethen cooled to ambient temperature
2. additionCelite (5 g) was added
3. stirringwith stirring
4. customthe solids were removed by filtration
5. washThe filtrate was washed with water (600 mL)
6. customThe organic layer was separated
7. extractionthe aqueous layer extracted with dichloromethane (3×100 mL)
8. dry with materialThe combined organic solution was dried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customto give a tan solid
12. customThe solid was chromatographed on silica with 3% methanol in dichloromethane

ORD record

ord-cd96d58b927444ec8d6288d90fccea82

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07538138B2