Reaktion #358572

Reaktionsgleichung

1-iodo-4-methylbenzene

ethyl bromo(difluoro)acetate

potassium hydrogen phosphate

→

title compound

Ausbeute 69.8%

ethyl difluoro(4-methylphenyl)acetate

Ausbeute 69.8%

Lösungsmittel

DMSO

water

isopropyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe compound was prepared by modification to the procedure of Sato, K
2. 2
   TemperaturAfter 14 h the reaction was cooled to room temperature
3. 3
   Temperaturcooled to 0° C.
4. 4
   FiltrationThe mixture was filtered through a pad of Celite
5. 5
   Waschenrinsing with isopropyl acetate
6. 6
   SonstigeThe phases were separated
7. 7
   Waschenthe aqueous layer was washed with isopropyl acetate
8. 8
   WaschenThe combined organic layers were washed with brine
9. 9
   Trocknendried (sodium sulfate)
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated
12. 12
    SonstigeThe residue was purified by silica gel chromatography (5% methylene chloride, 1-8% ethyl acetate/hexanes gradient)

Vorschrift

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.

Quelle