반응 #2286281

반응 방정식

hydrochloric acid

potassium carbonate

(3,5-dimethyl-4-hydroxy-phenyl)-acetic acid methyl ester

3,6-dichloro-4-isopropyl pyridazine

→

[4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-3,5-dimethyl-phenyl]-acetic acid methyl ester

수율 67.2%

[4-(6-Chloro-5-isopropyl-pyridazin-3-yloxy)-3,5-dimethyl-phenyl]-acetic acid methyl ester

수율 67.2%

용매

water

dimethyl sulfoxide

반응 조건

후처리

1. 1
   온도At this time, the reaction was cooled to room temperature
2. 2
   추출extracted with ethyl acetate (2×500 mL)
3. 3
   workup.ADDITIONby the addition of a 1N aqueous sodium hydroxide solution
4. 4
   추출The water layer was extracted again with ethyl acetate (1×500 mL)
5. 5
   세척The combined organics were washed with a saturated aqueous sodium chloride solution
6. 6
   건조dried with magnesium sulfate
7. 7
   여과filtered
8. 8
   농축concentrated under vacuum
9. 9
   기타The resulting residue was purified by column chromatography
10. 10
    세척eluted with 5-15% ethyl acetate in petroleum ether

실험 절차

A solution of (3,5-dimethyl-4-hydroxy-phenyl)-acetic acid methyl ester (6a) (12.5 g, 0.064 mol) in anhydrous dimethyl sulfoxide (256 mL) under argon at room temperature was treated with 3,6-dichloro-4-isopropyl pyridazine (7) (18.43 g, 0.096 mol) followed by anhydrous potassium carbonate (17.69 g, 0.12 mol) and copper (I) iodide (6.09 g, 0.032 mol). The reaction mixture was heated to 90° C. for 24 h. At this time, the reaction was cooled to room temperature and was poured onto a 1N aqueous hydrochloric acid solution (200 mL) and ice. The aqueous layer was diluted with water (100 mL) and extracted with ethyl acetate (2×500 mL). The aqueous layer was made basic (pH=8) by the addition of a 1N aqueous sodium hydroxide solution. The water layer was extracted again with ethyl acetate (1×500 mL). The combined organics were washed with a saturated aqueous sodium chloride solution, dried with magnesium sulfate, filtered and concentrated under vacuum. The resulting residue was purified by column chromatography using silica gel eluted with 5-15% ethyl acetate in petroleum ether to afford [4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-3,5-dimethyl-phenyl]-acetic acid methyl ester (8a) (15 g, 67%) and a minor amount of isomer as a white solid; EI(+)-HRMS m/z calcd for C18H21ClN2O3 (M+) 348.1241, found 348.1237. Molecular Weight=348.8327; Exact Mass=348.1241

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