Reaction #607461

Reaction equation

3-(2-chloroethyl) quinazoline-4 (3H)-one

sodium carbonate

sodium iodide

HCl

1-(3-(trifluoromethyl)phenyl)piperazine

→

3-(2-(4-(3-(trifluoromethyl)phenyl)piperazine-1-yl)ethyl)quinazoline-4 (3H)-one hydrochloride

Yield 69.0%

Solvents

isopropanol

ethanol

toluene

Conditions

Workup

1. 1
   workup.ADDITIONThe following were added to a 250 mL reactor
2. 2
   Otherwere removed slowly with the assistance of a Dean-Stark
3. 3
   workup.ADDITIONTo the resulting mixture, 100 mL of an aqueous solution of acetic acid were added at 10% and 150 mL of ethyl acetate
4. 4
   Otherthe organic phase separated
5. 5
   Washwashed with 2 portions of 50 mL of a 5% sodium bicarbonate solution
6. 6
   Dryingdry with MgSO4
7. 7
   Filtrationfiltered
8. 8
   Otherevaporated to dryness
9. 9
   Otheryielding the raw product as a slightly yellowish oil
10. 10
    TemperatureThis agitation was maintained for two hours in order
11. 11
    Otherthe precipitation of the hydrochloride
12. 12
    FiltrationThe resulting solid was filtered
13. 13
    Othervacuum dried

Procedure

The following were added to a 250 mL reactor: 3-(2-chloroethyl) quinazoline-4 (3H)-one (1 g, 4.79 mmol), 1-(3-(trifluoromethyl)phenyl)piperazine (1,103 g, 4.79 mmol), sodium carbonate (0.762 g, 7.19 mmol), sodium iodide (0.072 g, 0.479 mmol), ethanol (50 ml) and toluene (150 ml). The reaction medium was kept under agitation and reflux for a period of twenty hours, during which 150 ml of the solvent were removed slowly with the assistance of a Dean-Stark. To the resulting mixture, 100 mL of an aqueous solution of acetic acid were added at 10% and 150 mL of ethyl acetate. The mixture was agitated, the organic phase separated, washed with 2 portions of 50 mL of a 5% sodium bicarbonate solution, dry with MgSO4, filtered and evaporated to dryness, yielding the raw product as a slightly yellowish oil. This oil was dissolved in isopropanol, adding 2 mL of concentrated HCl under agitation to the resulting solution. This agitation was maintained for two hours in order to complete the precipitation of the hydrochloride. The resulting solid was filtered and vacuum dried, yielding 1.45 g of 3-(2-(4-(3-(trifluoromethyl)phenyl)piperazine-1-yl)ethyl)quinazoline-4 (3H)-one hydrochloride (3.3 mmol, yield=69%).

Source