Reaktion #2286290

Reaktionsgleichung

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

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

potassium tert-butoxide

3,6-dichloro-4-isopropyl pyridazine

→

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

Ausbeute 49.7%

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

Ausbeute 49.7%

Lösungsmittel

N,N-dimethyl acetamide

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeformed
2. 2
   workup.STIRRINGthe reaction mixture was stirred at 135° C. for 24 h
3. 3
   TemperaturThe reaction was cooled to room temperature
4. 4
   Extraktionextracted with tert-butyl methyl ether (1×600 mL)
5. 5
   Waschenwashed with a 1N aqueous sodium hydroxide solution (1×256 mL) and water (2×200 mL)
6. 6
   workup.DISTILLATIONThe organic layer was distilled to about 300 mL
7. 7
   workup.ADDITIONThe residue was treated with heptane (300 mL)
8. 8
   workup.STIRRINGThe mixture was stirred
9. 9
   Temperaturunder reflux for 30 min
10. 10
    Temperaturwas cooled to room temperature
11. 11
    FiltrationThe resulting solid was filtered
12. 12
    Waschenwashed with a 2:1 mixture of tert-butyl methyl ether
13. 13
    Trocknenheptane (240 mL) and dried overnight

Vorschrift

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

Quelle