Sodium Carbonate → Methyl 4-(4-bromo-2,3-difluorophenyl)-2-methylnicotinate

Temperatur

110 °C

In a microwave vessel, methyl 4-iodo-2-methylnicotinate (1.00 g, 3.61 mmol) was taken in a mixture of 1,4-dioxane (18 mL) and water (2 mL) under inert atmosphere. (4-bromo-2,3-difluorophenyl)boronic acid (1.03 g, 4.33 mmol) and Na2CO3 (765 mg, 7.22 mmol) were added to the reaction mixture and degassed for 5 minutes. Pd(Ph3P)4 (83 mg, 0.072 mmol) was added to the reaction mixture and heated in microwave at 110° C. for 90 min. The reaction mixture was diluted with water (150 mL) and extracted with ethyl acetate (200 mL). The organic phase was washed with brine (2×100 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (gradient of ethyl acetate and petroleum ether) to afford methyl 4-(4-bromo-2,3-difluorophenyl)-2-methylnicotinate (540 mg, 1.58 mmol, 44% yield) as a yellow liquid. LC/MS (ESI) m/e 344.0 [(M+2H)+, calcd for C14H12BrF2NO2 344.1]; LC/MS retention time (method C): tR=2.48 min.

1. customdegassed for 5 minutes
2. extractionextracted with ethyl acetate (200 mL)
3. washThe organic phase was washed with brine (2×100 mL)
4. dry with materialdried over Na2SO4
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by silica gel chromatography (gradient of ethyl acetate and petroleum ether)

ORD-Eintrag

ord-ef21628a521f46eb9062a224fb7da802

Quelldatensatz

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08901305B2