Tert-butyl 3-bromo-5-(2,2,2-trifluoro-1-hydroxyethyl)benzoate → Tert-butyl 3-(5-methylpyridin-2-yl)-5-(2,2,2-trifluoro-1-hydroxyethyl)benzoate

Temperature

70 °C

To a solution of tert-butyl 3-bromo-5-(2,2,2-trifluoro-1-hydroxyethyl)benzoate (5.0 g, 14.1 mmol) and bis(tri-tert-butylphosphine)palladium(0) (0.22 g, 0.42 mmol) in dioxane (70 mL) was added 5-methyl-2-pyridylzinc bromide (0.5 M in THF; 56.3 mL, 28.2 mmol). The reaction mixture was heated to 70° C. After 1 h, additional 5-methyl-2-pyridylzinc bromide (0.5 M in THF; 10 mL, 5.0 mmol) and bis(tri-tert-butylphosphine)palladium(0) (40 mg, 0.078 mmol) were added. After 30 min, the reaction was concentrated. Saturated aqueous sodium potassium tartrate tetrahydrate and saturated aqueous sodium bicarbonate were added. The mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→70% hexanes/ethyl acetate) gave the title compound. MS 368.2 (M+1).

1. waitAfter 30 min
2. concentrationthe reaction was concentrated
3. additionSaturated aqueous sodium potassium tartrate tetrahydrate and saturated aqueous sodium bicarbonate were added
4. extractionThe mixture was extracted with ethyl acetate (3×)
5. washThe combined organic extracts were washed with brine
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customPurification by silica gel chromatography (100% hexanes→70% hexanes/ethyl acetate)

ORD record

ord-84c672b5097f4cbe81c742a78935b181

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08247401B2