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

Temperatur

-78 °C

A RBF was charged with 3-chloro-4-ethyl-6-phenylpyridazine (250 mg, 1.143 mmol) and 5.7 mL of THF, and the mixture was cooled to −78° C. under nitrogen. Lithium diisopropylamide, 2.0 M solution in heptane/tetrahydrofuran/ethylbenzene (0.686 mL, 1.372 mmol) was added, and the mixture was stirred for 5 min at −78° C., followed by 1 h at room temperature. The mixture was cooled back down to −78° C., and methyl iodide (195 mg, 1.372 mmol) that had been passed through a plug of basic alumina prior to use was added dropwise. The reaction was stirred at this temperature for 5 min, followed by RT for 0.5 h. After quenching with water, the solution was diluted with CH2Cl2 and the layers were separated. The aqueous portion was extracted with additional CH2Cl2 and the combined organics were dried with MgSO4, filtered and concentrated. The crude material was purified by silica gel chromatography (CH2Cl2— 10% MeOH/CH2Cl2) to provide 3-chloro-4-isopropyl-6-phenylpyridazine as a colorless oil, which crystallized upon standing. MS m/z=233 [M+H]+. Calc'd for C13H13ClN2: 232.71.

1. waitfollowed by 1 h at room temperature
2. additionto use was added dropwise
3. stirringThe reaction was stirred at this temperature for 5 min
4. waitfollowed by RT for 0.5 h
5. customAfter quenching with water
6. additionthe solution was diluted with CH2Cl2
7. customthe layers were separated
8. extractionThe aqueous portion was extracted with additional CH2Cl2
9. dry with materialthe combined organics were dried with MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe crude material was purified by silica gel chromatography (CH2Cl2— 10% MeOH/CH2Cl2)

ORD-Eintrag

ord-75b936655985429a8879503fc92c46f9

Quelldatensatz

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08404694B2