Cesium carbonate → 3-Methyl-6-vinylpyridazine

Temperature

77.5 °C

Potassium vinyltrifluoroborate (Aldrich, 1.71 g, 12.7 mmol), 3-bromo-6-methylpyridazine (Example 148A, 1.95 g, 11.3 mmol) and triphenylphosphine (0.18 g, 0.67 mmol) were added at room temperature to a solution of Cs2CO3 (10.1 g, 31.0 mmol) in water (9.5 mL). Tetrahydrofuran (85 mL) was added, and the reaction flask was evacuated and purged with nitrogen (3 cycles). PdCl2 (50 mg, 0.28 mmol) was added, and the reaction flask was again evacuated and purged with nitrogen (3 cycles), then heated under nitrogen at 75-80° C. for 22 hours. The mixture was cooled to room temperature and the aqueous layer was separated and extracted with ethyl ether (3×50 mL). The combined organic phase was concentrated to a volume of approximately 5 mL, and the residue was purified by flash chromatography (80 g silica, eluted with hexanes-ethyl acetate, 100:0-90:10): 1H NMR (300 MHz, methanol-d4) δ ppm 2.71 (s, 3H) 5.63 (d, J=11.2 Hz, 1H) 6.18 (d, J=18.3 Hz, 1H) 7.04 (dd, J=17.8, 11.0 Hz, 1H) 7.23-7.34 (m, J=8.8 Hz, 1H) 7.49 (d, J=8.8 Hz, 1H).

1. customthe reaction flask was evacuated
2. custompurged with nitrogen (3 cycles)
3. customthe reaction flask was again evacuated
4. custompurged with nitrogen (3 cycles)
5. temperatureThe mixture was cooled to room temperature
6. customthe aqueous layer was separated
7. extractionextracted with ethyl ether (3×50 mL)
8. concentrationThe combined organic phase was concentrated to a volume of approximately 5 mL
9. customthe residue was purified by flash chromatography (80 g silica, eluted with hexanes-ethyl acetate, 100:0-90:10)

ORD record

ord-eaca9014d2b8438bbb7bc6316b8d8af1

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09063126B2