Reaktion #1944

Reaktionsgleichung

hydrochloric acid

sodium hydroxide

ethyl 8-(4-methylpiperazin-1-yl)-4H-quinolizin-4-one-3-carboxylate

→

desired product

8-(4-methylpiperazin-1-yl)-4H-quinolizin-4-one-3-carboxylic acid hydrochloride

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe THF was removed from the reaction mixture by distillation during the reaction
2. 2
   SonstigeThe concentrated reaction mixture
3. 3
   Temperaturwas cooled to ambient temperature
4. 4
   EinengenThe aqueous solution was concentrated in vacuo
5. 5
   Sonstigeto remove ~80% of the water
6. 6
   workup.ADDITIONthe concentrate was diluted with 50 mL of 95% ethyl alcohol
7. 7
   FiltrationThe solid was collected by filtration
8. 8
   Waschenwashed with 2 X 5 mL of ethyl alcohol
9. 9
   Sonstigedried in vacuo

Vorschrift

A mixture of 0.865 g (2.75 mmol) of ethyl 8-(4-methylpiperazin-1-yl)-4H-quinolizin-4-one-3-carboxylate, from Step 1, in 12 mL of THF and 16.5 mL of a 0.5N aqueous solution of sodium hydroxide was heated, with stirring, at 75° C. for 8 hours. The THF was removed from the reaction mixture by distillation during the reaction. The concentrated reaction mixture was cooled to ambient temperature and adjusted to pH 2.0 with 10.5 mL of 1N aqueous hydrochloric acid solution. The aqueous solution was concentrated in vacuo to remove ~80% of the water and the concentrate was diluted with 50 mL of 95% ethyl alcohol. The solid was collected by filtration, washed with 2 X 5 mL of ethyl alcohol and dried in vacuo to afford the desired product. The product was recrystallized from ethyl alcohol/water (3:1 v/v) to afford 0.332 g (37% yield) of the title compound, m.p.257°-258° C.; MS DCI-NH3 : 288 (M-Cl)+ 90%, 244 ((M-Cl)--CO2H)+ base, 270 (M-Cl--H2O)+ ; IR (KBr): 3420 (OH), 1645 (C=O) cm-1 ; 1H NMR (TFA) d 3.20 (m, 3H), 3.52 (dd, 2H, J=10 Hz), 4.02 (m, 4H), 4.63 (d, 2H, J=12 Hz), 7.41 (m, 2H), 7.65 (d, 1H, J=7.5 Hz), 8.26 (d, 1H, J=9 Hz), 9.18 (d, 1H, J=7.5 Hz). Analysis calculated for C15H18ClN3O3 +0.5H2O: C, 54.14; H, 5.75; N, 12.62. Found: C, 54.23; H, 5.54; N, 12.64.

Quelle