Methyl iodide → 3-Chloro-4-ethyl-6-phenylpyridazine

Temperature

-78 °C

A RBF was charged with 3-chloro-4-methyl-6-phenylpyridazine (5.0 g, 24 mmol) and 120 mL of THF under nitrogen, and the solution was cooled to −78° C. Lithium diisopropylamide, 2.0M in heptane/THF/ethylbenzene (15 ml, 29 mmol) was added and the mixture was stirred at −78° C. for 5 min, followed by RT for 1 h. The mixture was cooled to −78° C. and methyl iodide (1.8 ml, 29 mmol), which had been passed through a plug of basic alumina prior to use, was added dropwise. After stirring at −78° C. for 5 min, the reaction was stirred at RT for 0.5 h. Water was added to quench the reaction, and the mixture was concentrated and partitioned between dichloromethane and water. The layers were separated and the aqueous portion was extracted with additional DCM. The combined organics were dried with MgSO4, filtered and concentrated. The crude material was purified by silica gel chromatography (100% DCM to 95/5 DCM/MeOH) to provide 3-chloro-4-ethyl-6-phenylpyridazine as a tan solid. MS m/z=219 [M+H]+. Calc'd for C12H11ClN2: 218.68.

1. waitfollowed by RT for 1 h
2. temperatureThe mixture was cooled to −78° C.
3. additionwas added dropwise
4. stirringAfter stirring at −78° C. for 5 min
5. stirringthe reaction was stirred at RT for 0.5 h
6. customto quench
7. customthe reaction
8. concentrationthe mixture was concentrated
9. custompartitioned between dichloromethane and water
10. customThe layers were separated
11. extractionthe aqueous portion was extracted with additional DCM
12. dry with materialThe combined organics were dried with MgSO4
13. filtrationfiltered
14. concentrationconcentrated
15. customThe crude material was purified by silica gel chromatography (100% DCM to 95/5 DCM/MeOH)

ORD record

ord-8a3687ce27e4422298412b4f7a2dac1e

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08686155B2