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

HRID 1157216
ノート
印刷プレビュー

反応式

HRID 1157216 の反応式
[Br:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][OH:10])[CH:5]=[C:4]([Br: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.O>[Br:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][OH:10])[CH:5]=[C:4]([Br: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
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 140241623,6-Dichloro-4-isopropylpyridazineHCID 23665647Potassium tert-butoxideHCID 252604702,6-Dibromo-4-(2-hydroxyethyl)phenol

生成物 1

HCID 598344362-[3,5-Dibromo-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-phenyl]-ethanol収率 49.7%

試薬・触媒・溶媒 2

HCID 962Water溶媒
HCID 31374
Dimethylacetamide
溶媒

反応条件

温度
10 °C

実験手順

A mixture of 2,6-dibromo-4-(2-hydroxy-ethyl)-phenol (11) (183.3 g, 0.619 mol) in N,N-dimethyl acetamide (300 mL) was treated with potassium tert-butoxide (70.5 g, 0.59 mol) under nitrogen at room temperature. The suspension was heated to 10° C. and stirred until a solution formed. At this time, 3,6-dichloro-4-isopropyl pyridazine (7) (100 g, 0.50 mol) was added to the solution and the reaction mixture was stirred at 135° C. for 24 h. The reaction was cooled to room temperature, diluted with water (350 mL) and extracted with tert-butyl methyl ether (1×600 mL) followed by isopropyl acetate (1×600 mL). The organic layers were combined and washed with a 1N aqueous sodium hydroxide solution (1×256 mL) and water (2×200 mL). The organic layer was distilled to about 300 mL. The residue was treated with heptane (300 mL). The mixture was stirred under reflux for 30 min and then was cooled to room temperature. The resulting solid was filtered, washed with a 2:1 mixture of tert-butyl methyl ether: heptane (240 mL) and dried overnight to afford 2-[3,5-dibromo-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-phenyl]-ethanol (12) (112 g, 49%) as an off-white solid; LRMS for C15H15Br2ClN2O2 (M+) at m/z=450. Molecular Weight=450.5600; Exact Mass=447.9189

後処理

  1. customformed
  2. stirringthe reaction mixture was stirred at 135° C. for 24 h
  3. temperatureThe reaction was cooled to room temperature
  4. extractionextracted with tert-butyl methyl ether (1×600 mL)
  5. washwashed with a 1N aqueous sodium hydroxide solution (1×256 mL) and water (2×200 mL)
  6. distillationThe organic layer was distilled to about 300 mL
  7. additionThe residue was treated with heptane (300 mL)
  8. stirringThe mixture was stirred
  9. temperatureunder reflux for 30 min
  10. temperaturewas cooled to room temperature
  11. filtrationThe resulting solid was filtered
  12. washwashed with a 2:1 mixture of tert-butyl methyl ether
  13. dry with materialheptane (240 mL) and dried overnight

出典と根拠

ORDレコード
ord-481a20c821954884bea577f79f384507
出典データセット
uspto-grants-2010_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07807674B2

反応ノート

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