Hydrochloric Acid → [3-Chloro-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-5-methyl-phenyl]-acetic acid methyl ester

HRID 271157ノート

反応式

HRID 271157 の反応式
[CH3:1][O:2][C:3](=[O:14])[CH2:4][C:5]1[CH:10]=[C:9]([CH3:11])[C:8]([OH:12])=[C:7]([Cl:13])[CH:6]=1.[Cl:15][C:16]1[N:17]=[N:18][C:19](Cl)=[CH:20][C:21]=1[CH:22]([CH3:24])[CH3:23].C(=O)([O-])[O-].[K+].[K+].Cl>CS(C)=O.[Cu]I>[CH3:1][O:2][C:3](=[O:14])[CH2:4][C:5]1[CH:10]=[C:9]([CH3:11])[C:8]([O:12][C:19]2[N:18]=[N:17][C:16]([Cl:15])=[C:21]([CH:22]([CH3:24])[CH3:23])[CH:20]=2)=[C:7]([Cl:13])[CH:6]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 140241623,6-Dichloro-4-isopropylpyridazineHCID 68444019(3-Chloro-4-hydroxy-5-methyl-phenyl)-acetic acid methyl ester

生成物 1

HCID 86610363[3-Chloro-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-5-methyl-phenyl]-acetic acid methyl ester収率 81.2%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
90 °C

実験手順

A solution of 3-chloro-4-hydroxy-5-methyl-phenyl)-acetic acid methyl ester (6b) (909 mg, 0.004 mol) in anhydrous dimethyl sulfoxide (8 mL) under argon at room temperature was treated with 3,6-dichloro-4-isopropyl pyridazine (7) (1.2 g, 0.006 mol), anhydrous potassium carbonate (1.15 g, 0.008 mol) and copper (I) iodide (239 mg, 0.001 mol). The reaction mixture was heated to 90° C. overnight. At this time, the reaction mixture was cooled to room temperature, poured onto a 1N aqueous hydrochloric acid solution and was extracted with ethyl acetate. The 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 10% ethyl acetate in petroleum ether to afford [3-chloro-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-5-methyl-phenyl]-acetic acid methyl ester (8b) (1.2 g, 78%) as a yellow solid; EI(+)-HRMS m/z calcd for C17H18Cl2N2O3 (M+) 369.0767, found 369.0766. Molecular Weight=369.2506; Exact Mass=368.0694

後処理

  1. temperatureAt this time, the reaction mixture was cooled to room temperature
  2. extractionwas extracted with ethyl acetate
  3. washThe organics were washed with a saturated aqueous sodium chloride solution
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe resulting residue was purified by column chromatography
  8. washeluted with 10% ethyl acetate in petroleum ether

出典と根拠

ORDレコード
ord-31afca38680f45d2b0a881233cbc7374
出典データセット
uspto-grants-2008_11
特許番号
US07452882B2

反応ノート

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