2-(3,5-Dichloro-4-hydroxyphenyl)ethanol → 2-[3,5-Dichloro-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-phenyl]-ethanol

HRID 271164ノート

反応式

HRID 271164 の反応式
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][OH:10])[CH:5]=[C:4]([Cl:11])[C:3]=1[OH:12].CC(C)([O-])C.[K+].[Cl:19][C:20]1[N:21]=[N:22][C:23](Cl)=[CH:24][C:25]=1[CH:26]([CH3:28])[CH3:27]>CN(C)C(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][OH:10])[CH:5]=[C:4]([Cl:11])[C:3]=1[O:12][C:23]1[N:22]=[N:21][C:20]([Cl:19])=[C:25]([CH:26]([CH3:28])[CH3:27])[CH:24]=1

参加物

5

反応物 3

HCID 140187192-(3,5-Dichloro-4-hydroxyphenyl)ethanolHCID 140241623,6-Dichloro-4-isopropylpyridazineHCID 23665647Potassium tert-butoxide

生成物 1

HCID 598345252-[3,5-Dichloro-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-phenyl]-ethanol収率 44%

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
100 °C

実験手順

A mixture of 2,6-dichloro-4-(2-hydroxy-ethyl)-phenol (16) (12.5 g, 60.2 mmol) in N,N-dimethyl acetamide (28 mL) was treated with potassium tert-butoxide (6.5 g, 57.8 mmol) under nitrogen at room temperature. The suspension was heated to 100° C. and stirred until a solution formed. The reaction was then treated with 3,6-dichloro-4-isopropyl pyridazine (7) (9.2 g, 48 mmol) followed by a rinse with N,N-dimethyl acetamide (3 mL). The reaction mixture was stirred at 135° C. for 24 h. The reaction was cooled to room temperature, diluted with water (30 mL) and extracted with tert-butyl methyl ether (1×60 mL) followed by isopropyl acetate (1×60 mL). The organic layers were combined and were washed with a 1N aqueous sodium hydroxide solution (1×25 mL) and water (2×25 mL). The organic layer was separated and distilled to a volume of approximately 30 mL. This solution was treated with heptane (30 mL). The mixture was stirred under reflux for 30 min and then cooled to room temperature. The resulting solid was filtered, washed with ether and dried overnight to afford 2-[3,5-dichloro-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-phenyl]-ethanol (17) (7.5 g, 44%) as a white solid; LRMS for C15H15Cl3N2O2 (M+H) m/z=363. Molecular Weight=361.6580; Exact Mass=360.0199

後処理

  1. customformed
  2. washa rinse with N,N-dimethyl acetamide (3 mL)
  3. stirringThe reaction mixture was stirred at 135° C. for 24 h
  4. temperatureThe reaction was cooled to room temperature
  5. additiondiluted with water (30 mL)
  6. extractionextracted with tert-butyl methyl ether (1×60 mL)
  7. washwere washed with a 1N aqueous sodium hydroxide solution (1×25 mL) and water (2×25 mL)
  8. customThe organic layer was separated
  9. distillationdistilled to a volume of approximately 30 mL
  10. additionThis solution was treated with heptane (30 mL)
  11. stirringThe mixture was stirred
  12. temperatureunder reflux for 30 min
  13. temperaturecooled to room temperature
  14. filtrationThe resulting solid was filtered
  15. washwashed with ether
  16. customdried overnight

出典と根拠

ORDレコード
ord-eb970e3b8c6641ee9af36ab948c95e5e
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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