Reacción #657348

Ecuación de reacción

toluene

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

4-chlorophenylmagnesium bromide

→

title compound

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

Disolventes

ether

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroat 0° C.
2. 2
   Otrobefore being quenched with 1N HCl
3. 3
   ExtracciónThe aqueous layer was extracted with EtOAc (3×)
4. 4
   Lavadothe combined organics were washed with brine
5. 5
   Secadodried over Na2SO4
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated 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
    TemperaturaThe reaction mixture was refluxed for 2 h
11. 11
    Concentraciónbefore being concentrated under reduced pressure
12. 12
    FiltraciónThe resulting solid was filtered
13. 13
    Lavadowashed twice with ether
14. 14
    ExtracciónThe aqueous layer was extracted with EtOAc (3×)
15. 15
    Lavadothe combined organics were washed with brine
16. 16
    Secadodried over Na2SO4
17. 17
    Filtraciónfiltered
18. 18
    Concentraciónconcentrated under reduced pressure

Procedimiento

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.

Fuente