Reaktion #162355

Reaktionsgleichung

hydrochloric acid

1,2-diethyl 4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]tetrahydro-1,2-pyridazinedicarboxylate

product

1,2-diethyl 4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]tetrahydro-1,2-pyridazinedicarboxylate

potassium hydroxide

sodium bicarbonate

→

title compound

4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]hexahydropyridazine

Lösungsmittel

ethanol

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwas heated
2. 2
   Temperaturat reflux for 20 h
3. 3
   TemperaturThe reaction mixture was cooled
4. 4
   TemperaturThe reaction mixture was cooled
5. 5
   EinengenThe reaction mixture was concentrated under reduced pressure
6. 6
   Extraktionthe resulting matterial was extracted with diethyl ether (3×)
7. 7
   Trocknendried over magnesium sulfate
8. 8
   Filtrationfiltered
9. 9
   Einengenconcentrated under reduced pressure to a tan oil (2.99 g)
10. 10
    Sonstigeby purified by silica gel column chromatography (5% to 100% gradient of methanol in chloroform as eluant)

Vorschrift

A mixture of 1,2-diethyl 4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]tetrahydro-1,2-pyridazinedicarboxylate (i.e. the product of Step G) (4.09 g, 0.0083 mol) and potassium hydroxide (2.32 g, 0.0414 mol) in ethanol (50 mL) and water (5 mL) was heated at reflux for 20 h. The reaction mixture was cooled, acidified by the addition of concentrated hydrochloric acid, and then warmed to about 70° C. for 10 minutes. The reaction mixture was cooled, neutralised by the addition of sodium bicarbonate. The reaction mixture was concentrated under reduced pressure and the resulting matterial was extracted with diethyl ether (3×), dried over magnesium sulfate, filtered and concentrated under reduced pressure to a tan oil (2.99 g). The oil was adsorbed onto Celite® (diatomaceous filter aid), and then by purified by silica gel column chromatography (5% to 100% gradient of methanol in chloroform as eluant) to provide the title compound (1.275 g).

Quelle