Ethanol → 6-(4-Fluorophenyl)picolinic acid

Temperatur

100 °C

A solution of 2-bromo-picolinic acid (2.02 g, 10 mmol, Aldrich) in DME containing 4 mL of 10% aq. Na2CO3 was purged with Ar gas, treated with Pd(PPh3)4 followed by 2-(4-fluorophenyl)-5,5-dimethyl-1,3,2-dioxaborinane (2.40 g, 11.5 mmol, Aldrich) and EtOH (20 mL). This mixture was then also purged with Ar gas. The reaction mixture was heated at 100° C. for 2.5 h in a sealed tube. Additional 2-bromo-picolinic acid (900 mg) and Pd(PPh3)4 was added, and after purging with Ar gas it was heated at 100° C. for 4.5 h. Trifluoroacetic acid (20 mL) was added to the reaction and the mixture was concentrated in vacuo. MeOH (150 mL) was added to the residue and the insoluble material was filtered. The filtrate was concentrated in vacuo, and the resulting residue was purified by flash column chromatography on silica gel eluting with EtOAc/MeOH (9:1) followed by EtOAc/MeOH/HOAc (14:30:1) to afford the desired product (1.0 g, 40% based on borinane starting material) as a white solid. 1H NMR (CD3OD) δ 8.01 (d, 1H, J=7.7 Hz), 7.94–7.87 (m, 3H), 7.73 (d, 1H, J=7.7 Hz), 7.13 (t, 2H, J=8.8 Hz); MS(ESI+) m/z 234 (M+H)+.

1. customThis mixture was then also purged with Ar gas
2. additionAdditional 2-bromo-picolinic acid (900 mg) and Pd(PPh3)4 was added
3. customafter purging with Ar gas it
4. temperaturewas heated at 100° C. for 4.5 h
5. additionTrifluoroacetic acid (20 mL) was added to the reaction
6. concentrationthe mixture was concentrated in vacuo
7. additionMeOH (150 mL) was added to the residue
8. filtrationthe insoluble material was filtered
9. concentrationThe filtrate was concentrated in vacuo
10. customthe resulting residue was purified by flash column chromatography on silica gel eluting with EtOAc/MeOH (9:1)

ORD-Eintrag

ord-b9303d3f1b8b444da8f1484c9e9e9c1a

Quelldatensatz

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07173031B2