Reaktion #78458

Reaktionsgleichung

ammonium chloride

5-chloro-thiophene-2-carboxylic acid methoxy-methyl-amide

6-bromo-4-(3-chloro-phenyl)-2-methoxy-quinoline

lithium

→

title compound

Ausbeute 46.2%

[4-(3-Chloro-phenyl)-2-methoxy-quinolin-6-yl]-(5-chloro-thiophen-2-yl)-methanone

Ausbeute 46.2%

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto warm to ambient temperature
2. 2
   workup.STIRRINGstirred for 15 hours
3. 3
   SonstigeTHF was removed from the resulting heterogeneous solution
4. 4
   ExtraktionThe aqueous mixture was extracted with chloroform (CHCl3)
5. 5
   WaschenThe organic layer was washed with brine
6. 6
   Trocknendried over MgSO4
7. 7
   Einengenconcentrated under vacuum
8. 8
   Sonstigeto yield the crude product
9. 9
   SonstigeIt was chromatographed on silica gel with MeOH—CHCl3—NH4OH (2:98:0.2 to 5:95:0.5) as eluents

Vorschrift

To a solution of 6-bromo-4-(3-chloro-phenyl)-2-methoxy-quinoline (500 mg, 1.43 mmol) in THF (2 ml) was added n-buthyl lithium (2.5 M in hexane, 0.63 ml, 1.58 mmol) dropwise at −78° C. under an atmosphere of dry N2. After stirring at −78° C. for 30 minutes, a solution of 5-chloro-thiophene-2-carboxylic acid methoxy-methyl-amide (440 mg, 2.15 mmol) in THF (1 ml) was added. The reaction mixture was allowed to warm to ambient temperature and stirred for 15 hours. To the mixture was added a saturated aqueous solution of ammonium chloride at 0° C. THF was removed from the resulting heterogeneous solution. The aqueous mixture was extracted with chloroform (CHCl3). The organic layer was washed with brine, dried over MgSO4 and concentrated under vacuum to yield the crude product. It was chromatographed on silica gel with MeOH—CHCl3—NH4OH (2:98:0.2 to 5:95:0.5) as eluents to afford the title compound of example 40A (273.5 mg, 46% yield).

Quelle