Reacción #657337

Ecuación de reacción

6-[2-(3-fluoro-phenyl)-ethyl]-4H-benzo[1,4]oxazin-3-one

dimethylformamide

phosphorus(V) oxychloride

→

title compound

Rendimiento 67.0%

{3-Chloro-6-[2-(3-fluoro-phenyl)-ethyl]-benzo[1,4]oxazin-2-ylidenemethyl}-dimethyl-amine

Rendimiento 67.0%

Disolventes

chloroform

chloroform

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe reaction vessel was warmed to 23° C. for 10 min
2. 2
   Temperaturathen re-cooled to 0° C
3. 3
   workup.STIRRINGAfter stirring a further 5 min at 0° C. the reaction
4. 4
   Temperaturawas warmed
5. 5
   Temperaturato reflux (oil bath) for 4 h
6. 6
   Temperaturathen cooled to 23° C.
7. 7
   Otropartitioned between dichloromethane and water (100 mL each)
8. 8
   Otrothe organic layer was separated
9. 9
   LavadoThe organic layer was washed with brine (100 mL)
10. 10
    ExtracciónThe original aqueous layer was re-extracted with dichloromethane (100 mL)
11. 11
    Secadodried (MgSO4)
12. 12
    Filtraciónfiltered
13. 13
    Concentraciónconcentrated
14. 14
    OtroThe product was purified
15. 15
    Lavadothen eluted with ethyl acetate in heptane (0-40% ethyl acetate linear gradient over 16 column volumes at a flow rate of 60 mL/min)

Procedimiento

To a solution of dimethylformamide (0.82 mL, 10.6 mmol, 2.5 equiv) in chloroform (10 mL) at 0° C. was added phosphorus(V) oxychloride (0.78 mL, 8.49 mmol, 2 equiv). After stirring 10 min at 0° C., the reaction vessel was warmed to 23° C. for 10 min then re-cooled to 0° C. A solution of 6-[2-(3-fluoro-phenyl)-ethyl]-4H-benzo[1,4]oxazin-3-one in chloroform (7 mL) was added. After stirring a further 5 min at 0° C. the reaction was warmed to reflux (oil bath) for 4 h then cooled to 23° C. and partitioned between dichloromethane and water (100 mL each). The aqueous layer was adjusted to pH 12 with 5 N aqueous sodium hydroxide, and then the organic layer was separated. The organic layer was washed with brine (100 mL) and set aside. The original aqueous layer was re-extracted with dichloromethane (100 mL). The two organic extracts were combined, dried (MgSO4), filtered and concentrated. The product was purified using an Isco CombiFlash automated chromatography system. The residue was loaded onto a 80 g silica gel column as a solution in dichloromethane (5 mL) then eluted with ethyl acetate in heptane (0-40% ethyl acetate linear gradient over 16 column volumes at a flow rate of 60 mL/min) to give 985 mg (2.86 mmol, 67%) of the title compound as an orange/brown oil.

Fuente