Reacción #1605847

Ecuación de reacción

cesium carbonate

chloromethyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate

butyric acid

→

butyryloxymethyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate

Disolventes

ethyl acetate

dimethyl formamide

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroquenched with water/brine (1:1, 50 mL)
2. 2
   ExtracciónThe reaction was extracted with ethyl acetate (3×50 mL)
3. 3
   LavadoThe combined organics were washed with water (50 mL)
4. 4
   Secadobrine (50 mL) and dried (MgSO4)
5. 5
   Concentraciónconcentrated
6. 6
   OtroThe crude product was purified by column chromatography on silica eluting with 010% tetrahydrofuran/dichloromethane with 1% Et3N
7. 7
   Otroto give the product which
8. 8
   Otropurification
9. 9
   OtroThe product was purified by column chromatography on silica eluting with 0

Procedimiento

To a solution of chloromethyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate (1.20 g, 2.22 mmol) in dimethyl formamide (20 mL) was added butyric acid (0.30 mL, 3.33 mmol) followed by cesium carbonate (542 mg, 1.67 mmol). The reaction was then stirred at ambient temperature overnight. The reaction was diluted with ethyl acetate (50 mL) and quenched with water/brine (1:1, 50 mL). The reaction was extracted with ethyl acetate (3×50 mL). The combined organics were washed with water (50 mL) then brine (50 mL) and dried (MgSO4) and concentrated. The crude product was purified by column chromatography on silica eluting with 010% tetrahydrofuran/dichloromethane with 1% Et3N to give the product which required further purification. The product was purified by column chromatography on silica eluting with 0.51.5% Et3N/ethyl acetate to give butyryloxymethyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate, Compound-88 (348 mg, 26% over 2 steps).

Fuente