Реакция #2286294

Уравнение реакции

2,6-dichloro-4-(2-hydroxy-ethyl)-phenol

2,6-Dichloro-4-(2-hydroxy-ethyl)-phenol

potassium tert-butoxide

3,6-dichloro-4-isopropyl pyridazine

→

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

Выход 44.0%

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

Выход 44.0%

Растворители

N,N-dimethyl acetamide

Условия реакции

Обработка

1. 1
   Другоеformed
2. 2
   Промывкаa rinse with N,N-dimethyl acetamide (3 mL)
3. 3
   workup.STIRRINGThe reaction mixture was stirred at 135° C. for 24 h
4. 4
   ТемператураThe reaction was cooled to room temperature
5. 5
   workup.ADDITIONdiluted with water (30 mL)
6. 6
   Экстракцияextracted with tert-butyl methyl ether (1×60 mL)
7. 7
   Промывкаwere washed with a 1N aqueous sodium hydroxide solution (1×25 mL) and water (2×25 mL)
8. 8
   ДругоеThe organic layer was separated
9. 9
   workup.DISTILLATIONdistilled to a volume of approximately 30 mL
10. 10
    workup.ADDITIONThis solution was treated with heptane (30 mL)
11. 11
    workup.STIRRINGThe mixture was stirred
12. 12
    Температураunder reflux for 30 min
13. 13
    Температураcooled to room temperature
14. 14
    ФильтрацияThe resulting solid was filtered
15. 15
    Промывкаwashed with ether
16. 16
    Другоеdried overnight

Методика

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

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