Potassium Phosphate, Tribasic → HCID 58042484, compound

Temperature

80 °C

2-bromo-3-trifluoromethylpyridine (5 g, 22.1 mmol), cyclopropyl boronic acid (2.09 g, 24.3 mmol), and tribasic potassium phosphate (14.1 g, 66.4 mmol) were suspended in a mixture of toluene (150 mL) and water (30 mL), with rapid stirring. The suspension was heated to 80° C., and the solvent de-gassed by direct bubbling of N2 gas through the suspension for 30 minutes. The reaction was then heated to 95° C., and tricyclohexyl phosphine (620 mg, 2.21 mmol) followed by palladium acetate (248 mg, 1.12 mmol) were added. The reaction was left to stir and heat at 95° C. for 6 hours. The reaction was cooled to room temperature, and filtered through a plug of Arbocel™, eluting with ethyl acetate. The solvent was removed to leave a dark yellow oil. TBME was added (300 mL), and the organic phase washed with 2M HCl solution (3×200 mL). The organics were discarded. TBME (300 mL) was added to the combined aqueous layers, and solid sodium bicarbonate was added until the aqueous layer reached pH 7. The organic layer was removed, and the aqueous layer was extracted with TBME (2×100 mL). The combined organic extracts were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 4:1 heptane:ethyl acetate, affording the title compound as a colourless oil (400 mg, 10%).

1. customthe solvent de-gassed
2. customby direct bubbling of N2 gas through the suspension for 30 minutes
3. temperatureThe reaction was then heated to 95° C.
4. additionwere added
5. waitThe reaction was left
6. temperatureheat at 95° C. for 6 hours
7. temperatureThe reaction was cooled to room temperature
8. filtrationfiltered through a plug of Arbocel™
9. washeluting with ethyl acetate
10. customThe solvent was removed
11. customto leave a dark yellow oil
12. washthe organic phase washed with 2M HCl solution (3×200 mL)
13. additionTBME (300 mL) was added to the combined aqueous layers, and solid sodium bicarbonate
14. additionwas added until the aqueous layer
15. customThe organic layer was removed
16. extractionthe aqueous layer was extracted with TBME (2×100 mL)
17. dry with materialThe combined organic extracts were dried over magnesium sulfate
18. filtrationfiltered
19. concentrationconcentrated in vacuo
20. customThe residue was purified by silica gel column chromatography
21. washeluting with 4:1 heptane

ORD record

ord-4672348269454f2093a1278bc4f21de7

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592629B2