Diethyl Ether → 4-(Tert-butyl)-2-(5,6-dichloropyridin-3-yl)phenol

Temperature

80 °C

A mixture of 5-(tert-butyl)-2-((2-methoxyethoxy)methoxy)benzeneboronic acid (Intermediate 7) (1.0 g, 3.54 mmol), 5-bromo-2,3-dichloropyridine (0.80 g, 3.53 mmol) and potassium carbonate (1.5 g, 10.85 mmol) in DME (20 mL) and water (5 mL) was purged with nitrogen for 20 minutes. Tetrakis(triphenylphosphine)palladium (0) (200.0 mg, 0.17 mmol) was added and the mixture heated at 80° C. overnight. The cooled reaction mixture was extracted with ethyl acetate (50 mL), the organic phase separated, dried (MgSO4), filtered and concentrated under reduced pressure. The product was purified using flash chromatography on silica eluting with 30% ethyl acetate in hexanes to give the MEM ether intermediate. The MEM ether was stirred in 10% hydrochloric acid in ethanol at room temperature for 4 hours. The reaction mixture was then concentrated under reduced pressure to give 4-(tert-butyl)-2-(5,6-dichloropyridin-3-yl)phenol.

1. customwas purged with nitrogen for 20 minutes
2. customThe cooled reaction mixture
3. extractionwas extracted with ethyl acetate (50 mL)
4. customthe organic phase separated
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe product was purified
9. customto give the MEM ether intermediate
10. concentrationThe reaction mixture was then concentrated under reduced pressure

ORD record

ord-9e51096da5d54d32a11f1c3c512e2d75

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09409893B2