Reacción #445985

Ecuación de reacción

2-phenylamino-4-hydroxymethyl-6-cyclopropylpyrimidine

diethylaminosulfur trifluoride

sodium hydrogen carbonate

carbon dioxide

→

2-PHENYLAMINO-4-FLUOROMETHYL-6-CYCLOPROPYLPYRIMIDINE

Disolventes

dichloromethane

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONare added dropwise
2. 2
   Otrothe organic phase is separated off
3. 3
   Extracciónthe aqueous phase is extracted twice with 20 ml of dichloromethane each time
4. 4
   LavadoThe combined dichloromethane solutions are washed with 15 ml of water
5. 5
   Secadodried over sodium sulfate
6. 6
   Filtraciónfiltered
7. 7
   Otrothe solvent is evaporated
8. 8
   OtroThe black oil which remains is purified by column chromatography over silica gel (toluene/chloroform/diethyl ether/petroleum ether (b.p. 50°-70° ); 5/3/1/1)
9. 9
   OtroAfter the eluant mixture has been evaporated off
10. 10
    workup.ADDITIONthe yellow oil is diluted with 20 ml of petroleum ether (b.p. 50°-70° C.)
11. 11
    Otrocrystallised at reduced temperature
12. 12
    Otromelt at 50°-52° C
13. 13
    Otro53% of the theoretical yield)

Procedimiento

6.1 g (37.8 mmol) of diethylaminosulfur trifluoride in 15 ml of dichloromethane are slowly added dropwise within a period of one hour, with stirring, to a suspension of 9.1 g (37.8 mmol) of 2-phenylamino-4-hydroxymethyl-6-cyclopropylpyrimidine in 80 ml of dichloromethane. After the addition of 50 ml of ice-water, 50 ml of 10% aqueous sodium hydrogen carbonate solution are added dropwise. When the evolution of carbon dioxide has ceased, the organic phase is separated off and the aqueous phase is extracted twice with 20 ml of dichloromethane each time. The combined dichloromethane solutions are washed with 15 ml of water, dried over sodium sulfate and filtered, and the solvent is evaporated. The black oil which remains is purified by column chromatography over silica gel (toluene/chloroform/diethyl ether/petroleum ether (b.p. 50°-70° ); 5/3/1/1). After the eluant mixture has been evaporated off, the yellow oil is diluted with 20 ml of petroleum ether (b.p. 50°-70° C.) and crystallised at reduced temperature. The yellowish crystals melt at 50°-52° C. Yield: 4.9 g (20.1 mmol; 53% of the theoretical yield).

Fuente