Reacción #162351

Ecuación de reacción

hydrochloric acid

5-(2,6-difluorophenyl)-4,5-dihydro-N,N-dimethyl-3-isoxazolecarboxamide

methyl magnesium bromide

5-(2,6-difluorophenyl)-4,5-dihydro-N,N-dimethyl-3-isoxazolecarboxamide

product

5-(2,6-difluorophenyl)-4,5-dihydro-N,N-dimethyl-3-isoxazolecarboxamide

toluene

→

title compound

1-(4,5-dihydro-5-(2,6-difluorophenyl)-3-isoxazolyl)ethanone

Disolventes

water

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroTo a 1 L flask equipped with a thermometer and addition funnel
2. 2
   Temperaturawhile maintaining the temperature between −10 and −5° C
3. 3
   Temperaturawhile maintaining the temperature between 10 and 30° C
4. 4
   OtroThe organic layer was separated
5. 5
   Lavadowashed with saturated aqueous sodium chloride solution (80 mL)
6. 6
   Concentraciónconcentrated under reduced pressure
7. 7
   OtroThe resulting oil was crystallized from hexanes (100 mL)
8. 8
   Filtracióncollected by filtration
9. 9
   Lavadowashed with hexanes
10. 10
    Otrodried in a vacuum oven overnight at 23° C.

Procedimiento

To a 1 L flask equipped with a thermometer and addition funnel was added 5-(2,6-difluorophenyl)-4,5-dihydro-N,N-dimethyl-3-isoxazolecarboxamide (i.e. the product of Step A) (80.0 g, 0.31 mol) and toluene (320 mL). The reaction mixture was cooled to −5° C., and methyl magnesium bromide (3.0 M in tetrahydrofuran, 120 mL, 0.36 mmol) was added dropwise while maintaining the temperature between −10 and −5° C. When gas chromatography analysis of the reaction mixture showed about 2% of 5-(2,6-difluorophenyl)-4,5-dihydro-N,N-dimethyl-3-isoxazolecarboxamide remaining, the reaction mixture was poured into a stirred solution of concentrated hydrochloric acid (80 mL) and water (320 mL) while maintaining the temperature between 10 and 30° C. The organic layer was separated, washed with saturated aqueous sodium chloride solution (80 mL), and then concentrated under reduced pressure. The resulting oil was crystallized from hexanes (100 mL), collected by filtration, washed with hexanes, and dried in a vacuum oven overnight at 23° C. to provide the title compound as a waxy, off-white solid (65 g), melting at 47-50° C.

Fuente