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

HRID 271151ノート

反応式

HRID 271151 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]([CH3:13])[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.O.[Cu]I>[CH3:1][O:2][C:3](=[O:14])[CH2:4][C:5]1[CH:6]=[C:7]([CH3:13])[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:9]([CH3:11])[CH:10]=1

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 140241623,6-Dichloro-4-isopropylpyridazineHCID 20582798(3,5-Dimethyl-4-hydroxy-phenyl)-acetic acid methyl ester

生成物 1

HCID 59834457[4-(6-Chloro-5-isopropyl-pyridazin-3-yloxy)-3,5-dimethyl-phenyl]-acetic acid methyl ester収率 67.2%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒

反応条件

温度
90 °C

実験手順

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

後処理

  1. temperatureAt this time, the reaction was cooled to room temperature
  2. extractionextracted with ethyl acetate (2×500 mL)
  3. additionby the addition of a 1N aqueous sodium hydroxide solution
  4. extractionThe water layer was extracted again with ethyl acetate (1×500 mL)
  5. washThe combined organics were washed with a saturated aqueous sodium chloride solution
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe resulting residue was purified by column chromatography
  10. washeluted with 5-15% ethyl acetate in petroleum ether

出典と根拠

ORDレコード
ord-7513d5be653445f48318409ea1a41343
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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