Reaction #657348

Reaction equation

toluene

2-methyl-6-(methyloxy)-4H-3,1-benzoxazin-4-one

4-chlorophenylmagnesium bromide

→

title compound

[2-amino-5-(methyloxy)phenyl](4-chlorophenyl)methanone

Solvents

ether

Conditions

Workup

1. 1
   Otherat 0° C.
2. 2
   Otherbefore being quenched with 1N HCl
3. 3
   ExtractionThe aqueous layer was extracted with EtOAc (3×)
4. 4
   Washthe combined organics were washed with brine
5. 5
   Dryingdried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated under reduced pressure
8. 8
   workup.DISSOLUTIONThe crude compound was then dissolved in EtOH (400 mL)
9. 9
   workup.ADDITION6N HCl (160 mL) was added
10. 10
    TemperatureThe reaction mixture was refluxed for 2 h
11. 11
    Concentrationbefore being concentrated under reduced pressure
12. 12
    FiltrationThe resulting solid was filtered
13. 13
    Washwashed twice with ether
14. 14
    ExtractionThe aqueous layer was extracted with EtOAc (3×)
15. 15
    Washthe combined organics were washed with brine
16. 16
    Dryingdried over Na2SO4
17. 17
    Filtrationfiltered
18. 18
    Concentrationconcentrated under reduced pressure

Procedure

To a solution of 2-methyl-6-(methyloxy)-4H-3,1-benzoxazin-4-one (for a preparation see Intermediate 8) (40.0 g, 0.21 mol) in a toluene (560 mL)/ether (200 mL) mixture at 0° C. was added dropwise a solution of 4-chlorophenylmagnesium bromide (170 mL, 1M in Et2O, 0.17 mol). The reaction mixture was allowed to warm to RT and stirred for 1 h before being quenched with 1N HCl. The aqueous layer was extracted with EtOAc (3×) and the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude compound was then dissolved in EtOH (400 mL) and 6N HCl (160 mL) was added. The reaction mixture was refluxed for 2 h before being concentrated under reduced pressure. The resulting solid was filtered and washed twice with ether before being suspended in EtOAc and neutralised with 1N NaOH. The aqueous layer was extracted with EtOAc (3×) and the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The title compound was obtained as a yellow solid (39 g, 88% yield) which was used without further purification.

Source