Reaktion #315019

Reaktionsgleichung

methyl iodide

Lithium diisopropylamide

heptane THF ethylbenzene

3-chloro-4-methyl-6-phenylpyridazine

→

3-chloro-4-ethyl-6-phenylpyridazine

Lösungsmittel

THF

Water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITfollowed by RT for 1 h
2. 2
   TemperaturThe mixture was cooled to −78° C.
3. 3
   workup.ADDITIONwas added dropwise
4. 4
   workup.STIRRINGAfter stirring at −78° C. for 5 min
5. 5
   workup.STIRRINGthe reaction was stirred at RT for 0.5 h
6. 6
   Sonstigeto quench
7. 7
   Sonstigethe reaction
8. 8
   Einengenthe mixture was concentrated
9. 9
   Sonstigepartitioned between dichloromethane and water
10. 10
    SonstigeThe layers were separated
11. 11
    Extraktionthe aqueous portion was extracted with additional DCM
12. 12
    TrocknenThe combined organics were dried with MgSO4
13. 13
    Filtrationfiltered
14. 14
    Einengenconcentrated
15. 15
    SonstigeThe crude material was purified by silica gel chromatography (100% DCM to 95/5 DCM/MeOH)

Vorschrift

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.

Quelle