Reacción #358572

Ecuación de reacción

1-iodo-4-methylbenzene

ethyl bromo(difluoro)acetate

potassium hydrogen phosphate

→

title compound

Rendimiento 69.8%

ethyl difluoro(4-methylphenyl)acetate

Rendimiento 69.8%

Disolventes

DMSO

water

isopropyl acetate

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe compound was prepared by modification to the procedure of Sato, K
2. 2
   TemperaturaAfter 14 h the reaction was cooled to room temperature
3. 3
   Temperaturacooled to 0° C.
4. 4
   FiltraciónThe mixture was filtered through a pad of Celite
5. 5
   Lavadorinsing with isopropyl acetate
6. 6
   OtroThe phases were separated
7. 7
   Lavadothe aqueous layer was washed with isopropyl acetate
8. 8
   LavadoThe combined organic layers were washed with brine
9. 9
   Secadodried (sodium sulfate)
10. 10
    Filtraciónfiltered
11. 11
    Concentraciónconcentrated
12. 12
    OtroThe residue was purified by silica gel chromatography (5% methylene chloride, 1-8% ethyl acetate/hexanes gradient)

Procedimiento

The compound was prepared by modification to the procedure of Sato, K.; Kawata, R.; Ama, F.; Omote, M.; Ando, A. Chemical & Pharmaceutical Bulletin 47(7), 1013-1016 (1999). To a solution of 1-iodo-4-methylbenzene (25.1 g, 115 mmol) in DMSO (125 mL) was added ethyl bromo(difluoro)acetate (24.7 g, 122 mmol) and copper (16.8 g, 264 mmol), and the resulting solution was heated to 55° C. After 14 h the reaction was cooled to room temperature and diluted with isopropyl acetate, then cooled to 0° C. and treated with a solution of potassium hydrogen phosphate (23.3 g) in water (250 mL). The mixture was filtered through a pad of Celite, rinsing with isopropyl acetate. The phases were separated and the aqueous layer was washed with isopropyl acetate. The combined organic layers were washed with brine, dried (sodium sulfate), filtered and concentrated. The residue was purified by silica gel chromatography (5% methylene chloride, 1-8% ethyl acetate/hexanes gradient) gave the title compound (17.2 g) as an oil.

Fuente