Potassium Fluoride → HCID 58042336, compound

Temperature

80 °C

4-Bromo-3-chlorophenol (518 mg, 2.5 mmol), 3-(trifluoromethyl)phenylboronic acid (617 mg, 3.25 mmol), potassium fluoride (435 mg, 7.5 mmol) palladium acetate (28 mg, 0.125 mmol) and S_phos (102 mg, 0.25 mmol) were stirred in dioxane (10 mL) at 80° C. for 4 hours. The reaction mixture was partitioned between ethyl acetate (100 mL) and water (50 mL). The EtOAc was dried over MgSO4 and evaporated. The residue was resubjected to the reaction conditions and was redissolved in dioxane (10 mL). 3-(trifluoromethyl)phenylboronic acid (380 mg, 2 mmol), potassium fluoride (348 mg, 6 mmol) palladium acetate (14 mg, 0.0625 mmol) and S_phos (51 mg, 0.125 mmol) were added and the reaction stirred at 80° C. for a further 4 hours. The reaction mixture was worked up as before and the crude product was chromatographed on silica eluting with a gradient of heptane:ethyl acetate 100:0 to 75:25. Fractions containing product were evaporated. The resulting material was chromatographed on silica eluting with a gradient of cyclohexane:triethylamine:isopropyl alcohol 95:5:0 to 95:5:10 to give the title compound (310 mg, 1.14 mmol, 45%) as a colourless gum.

1. customThe reaction mixture was partitioned between ethyl acetate (100 mL) and water (50 mL)
2. dry with materialThe EtOAc was dried over MgSO4
3. customevaporated
4. customThe residue was resubjected to the reaction conditions
5. customwas chromatographed on silica eluting with a gradient of heptane:ethyl acetate 100:0 to 75:25
6. additionFractions containing product
7. customwere evaporated
8. customThe resulting material was chromatographed on silica eluting with a gradient of cyclohexane:triethylamine:isopropyl alcohol 95:5:0 to 95:5:10

ORD record

ord-ddf5d67de5734aaf9b9756013f583a55

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772293B2