Reaction #2487447

Reaction equation

2-(4-chlorophenyl)-7-trifluoromethyl-3H-quinazolin-4-one

phosphorus oxychloride

→

4-Chloro-2-(4-chloro-phenyl)-7-trifluoromethylquinazoline

Solvents

dioxane

Conditions

Workup

1. 1
   TemperatureThe suspension was then heated
2. 2
   Temperatureat reflux for 2 h
3. 3
   Otherevaporated under reduced pressure
4. 4
   workup.DISSOLUTIONThe remaining solid was dissolved in dioxane (1 L)
5. 5
   workup.ADDITIONan aqueous solution of sodium hydroxide (50 mL, 10% weight/weight (w/w)) was added dropwise
6. 6
   Temperaturemaintaining the internal temperature≦10° C.)
7. 7
   workup.ADDITIONWater (1 L) was then added to the resultant suspension
8. 8
   workup.ADDITIONfollowed by the dropwise addition of a further quantity of aqueous sodium hydroxide (90 mL, 10% w/w)
9. 9
   OtherThe precipitate was isolated by vacuum filtration
10. 10
    Washwashing with water (3×500 mL)
11. 11
    Otherdried under vacuum (10 mbar, 50° C.)
12. 12
    Other4.7 min, 343 (M+)

Procedure

To a stirred suspension of 2-(4-chlorophenyl)-7-trifluoromethyl-3H-quinazolin-4-one (50 g, 0.15 mol) in dioxane (400 mL) was added dropwise phosphorus oxychloride (43 mL, 0.46 mol). The suspension was then heated at reflux for 2 h then allowed to cool to room temperature and evaporated under reduced pressure. The remaining solid was dissolved in dioxane (1 L) and an aqueous solution of sodium hydroxide (50 mL, 10% weight/weight (w/w)) was added dropwise maintaining the internal temperature≦10° C.). Water (1 L) was then added to the resultant suspension followed by the dropwise addition of a further quantity of aqueous sodium hydroxide (90 mL, 10% w/w). The precipitate was isolated by vacuum filtration washing with water (3×500 mL) and dried under vacuum (10 mbar, 50° C.). Yield=49 g, 93%; LC-MS: 4.7 min, 343 (M+); 1H NMR (dimethylsulfoxide (DMSO)-d6) δ 7.68 (d, 2 H, J=8.9 Hz), 8.12 (dd, 1 H, J=8.9, 1.8 Hz), 8.48-8.54 (m, 4 H).

Source