Water → HCID 69673041, compound

Temperature

80 °C

A mixture of 4-bromo-6-(trifluoromethyl)pyridine-2-carboxylic acid (0.50 g, 1.8 mmol, Anichem), (2-Ethenyl)tri-n-butyltin (919 μL, 3.14 mmol, Aldrich) and tetrakis(triphenylphosphine)palladium(0) (428 mg, 0.370 mmol, Strem) in toluene (4.2 mL) was degassed by a stream of nitrogen through the solution for 15 minutes. Triethylamine (774 μL, 5.56 mmol) was added and the mixture was heated to 80° C. for 2 hours. After cooling to ambient temperature, water and 1N NaOH were added and the product was extracted with four portions of ethyl acetate. The aqueous layer was then treated with 1N HCl to achieve a pH between 4 and 5, and was extracted with six portions of 10% isopropanol in chloroform. The combined organic extracts were dried over sodium sulfate, filtered and concentrated to afford crude product, which was used without further purification in Step B. H NMR (300 MHz, CDCl3) δ 8.40 (d, J=1.3 Hz, 1H), 7.88 (d, J=1.5 Hz, 1H), 6.82 (dd, J=17.6, 10.9 Hz, 1H), 6.23 (d, J=17.4 Hz, 1H), 5.78 (d, J=10.9 Hz, 1H); LCMS (M+H)+: 218.1.

1. customwas degassed by a stream of nitrogen through the solution for 15 minutes
2. temperatureAfter cooling to ambient temperature
3. extractionthe product was extracted with four portions of ethyl acetate
4. additionThe aqueous layer was then treated with 1N HCl
5. extractionwas extracted with six portions of 10% isopropanol in chloroform
6. dry with materialThe combined organic extracts were dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customto afford crude product, which
10. customwas used without further purification in Step B

ORD record

ord-120b6d2e6ab04b4c8b22f6d8b7f4c213

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08933085B2