反应 #2286281

反应方程式

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

收率 67.2%

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

收率 67.2%

溶剂

water

dimethyl sulfoxide

反应条件

后处理

1. 1
   温度At this time, the reaction was cooled to room temperature
2. 2
   萃取extracted with ethyl acetate (2×500 mL)
3. 3
   workup.ADDITIONby the addition of a 1N aqueous sodium hydroxide solution
4. 4
   萃取The water layer was extracted again with ethyl acetate (1×500 mL)
5. 5
   洗涤The combined organics were washed with a saturated aqueous sodium chloride solution
6. 6
   干燥dried with magnesium sulfate
7. 7
   过滤filtered
8. 8
   浓缩concentrated under vacuum
9. 9
   其他The resulting residue was purified by column chromatography
10. 10
    洗涤eluted with 5-15% ethyl acetate in petroleum ether

实验过程

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

来源