Tetrahydrofuran → 3-(3,5-Difluorophenyl)picolinaldehyde

Temperatur

90 °C

To a solution of 3-bromo-pyridine-2-carbaldehyde (1.2 g, 6.45 mmol) dissolved in ethylene glycol dimethyl ether (25 mL), THF (10 mL) and saturated solution of Na2CO3 (9 mL) was added 3,5 difluorophenyl boronic acid (1.12 g, 7.10 mmol). Purge the mixture with Ar gas (10 min). To this mixture was added Pd(PPh3)4 (373 mg, 0.33 mmol) and stir under a positive pressure of Ar at 90° C. for 16 hours. The reaction mixture was quenched with a solution of saturated NaHCO3 (50 mL). Extract with CH2Cl2 (2×50 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo to afford a light yellow oil. Purification via column chromatography on silica gel (CH2Cl2:MeOH: 80:20, v/v/v) afforded 3-(3,5-difluoro-phenyl)-pyridine-2-carbaldehyde as a white solid (0.86 g, 61%). 1H NMR (CDCl3) δ 6.59 (m, 1H), 6.92 (m, 2H), 7.60 (m, 1H), 7.76 (d, 1H, J=7.5 Hz), 8.88 (d, 1H, J=3.5 Hz), 10.11 (s, 1H).

1. customPurge the mixture with Ar gas (10 min)
2. customThe reaction mixture was quenched with a solution of saturated NaHCO3 (50 mL)
3. extractionExtract with CH2Cl2 (2×50 mL)
4. dry with materialThe combined organic extracts were dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customto afford a light yellow oil
8. customPurification via column chromatography on silica gel (CH2Cl2:MeOH: 80:20, v/v/v)

ORD-Eintrag

ord-a35dd64a074b4a8abc7746b8a7990a24

Quelldatensatz

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07863293B2