3,5-Dichloropyridazine → 5-Chloro-3-(4-fluorophenyl)pyridazine

Temperature

-65 °C

To a mixture of S-chloropyridazin-3(2H)-one (7.33 g, 56 mmol) was suspended in phosphorous oxychloride (55 ml, 594 mmol) and the mixture was heated at 80° C. for 3 hours. After cooling to room temperature the homogeneous dark solution was evaporated under reduced pressure and repartitioned between chloroform and water (50 ml each). The pH was adjusted to 8 by portionwise addition of saturated aqueous sodium carbonate solution and the phases were separated. After two further extractions the combined organic extracts were washed with water and brine and dried over sodium sulfate. After filtration the compound was adsorbed onto silica gel and purified by flash column (10% ethyl acetate-iso-hexane) to yield 3,5-dichloropyridazine (5.6 g, 67%) as a pale yellow solid. A sample of 3,5-dichloropyridazine (0.43 g, 2.9 mmol) was dissolved in tetrahydrofuran (10 ml) under nitrogen and cooled to −65° C. 1,2-(Bis(diphenylphosphino)ethane)-dichloronickel(II) (0.08 g, 0.15 mmol) was added followed by 4-fluorophenylzinc bromide (11.6 ml of a 0.5 M solution in tetrahydrofuran). The mixture was warmed to −10° C. over 4 hours and poured onto a mixture of ethyl acetate/water (30 ml/10 ml). The phases were separated and the aqueous phase was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and adsorbed onto silica gel. Purification by flask column chromatography (10% ethyl acetate-iso-hexane) gave the title compound (0.35 g, 58%) as a red solid.

1. temperatureThe mixture was warmed to −10° C. over 4 hours
2. customThe phases were separated
3. extractionthe aqueous phase was extracted twice with ethyl acetate
4. washThe combined organic layers were washed with brine
5. dry with materialdried over sodium sulfate
6. customPurification by flask column chromatography (10% ethyl acetate-iso-hexane)

ORD record

ord-73b31729cbe545d5b1dd461e43d63314

Source dataset

uspto-grants-2008_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07442701B2