Phosphoric Acid → Methyl 4-(4-chloro-2-fluoro-3-methoxyphenyl)-2-methylnicotinate

Temperatur

100 °C

A mixture of methyl 4-chloro-2-methylnicotinate (1.5 g, 8.08 mmol), 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.316 g, 8.08 mmol), phosphoric acid, potassium salt (3.43 g, 16.16 mmol) and PdCl2(dppf)-CH2Cl2 adduct (0.660 g, 0.808 mmol) in 1,4-dioxane (25 mL) and water (5 mL) was purged with nitrogen for 5 min. The reaction was then heated to 100° C. for 18 h. After cooling, the reaction was diluted with water (50 mL) and extracted with ethyl acetate (2×75 mL). The combined organic layers were washed with brine solution, dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography using 50% ethyl acetate in hexanes to yield methyl 4-(4-chloro-2-fluoro-3-methoxyphenyl)-2-methylnicotinate (1.2 g, 2.52 mmol, 31% yield) as pale brown oil. LC/MS (ESI) m/e 309.9 [(M+H)+, calcd for C15H14ClFNO3 310.1]; LC/MS retention time (method D): tR=0.84 min.

1. customwas purged with nitrogen for 5 min
2. temperatureAfter cooling
3. additionthe reaction was diluted with water (50 mL)
4. extractionextracted with ethyl acetate (2×75 mL)
5. washThe combined organic layers were washed with brine solution
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by silica gel chromatography

ORD-Eintrag

ord-ecca1684e53e4cb092a918d5c103bd5f

Quelldatensatz

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08901305B2