反応 #4012

反応方程式

sodium

2-amino-4-chloro-6-chloromethyl-pyrimidine

2,2,2-trifluoro-ethanol

sodium

2,2,2-trifluoroethanol

sodium

2,2,2-trifluoroethanol

→

2-amino-4-chloromethyl-6-(2,2,2-trifluoroethoxy)pyrimidine

反応条件

後処理

1. 1
   温度ice-bath cooling
2. 2
   workup.DISSOLUTIONdissolved
3. 3
   workup.STIRRINGthe resulting mixture was stirred at 60° C. for 18 hours
4. 4
   workup.ADDITIONadded to the reaction mixture
5. 5
   workup.STIRRINGStirring at 60° C.
6. 6
   温度the reaction mixture was cooled
7. 7
   その他evaporated in vacuo
8. 8
   その他The residue was partitioned between ethyl acetate and water
9. 9
   その他The organic layer was separated
10. 10
    洗浄washed with water
11. 11
    乾燥dried (MgSO4)
12. 12
    その他evaporated
13. 13
    その他The crude product was purified by chromatography on silica (Merck Kieselgel 60 using
14. 14
    workup.ADDITIONa 50:50 mixture of ether and 40°-60° petroleum ether as eluent
15. 15
    その他followed by recrystallisation from a mixture of 60°-80° petroleum ether and ethyl acetate

実験手順

0.23 Parts of sodium metal was added to 10 parts of 2,2,2-trifluoroethanol with stirring and ice-bath cooling. The mixture was then stirred for several hours at room temperature until the sodium dissolved. This solution was added dropwise, over 30 minutes, to a stirred suspension of 1.78 parts of 2-amino-4-chloro-6-chloromethyl-pyrimidine in 25 parts of 2,2,2-trifluoro-ethanol and the resulting mixture was stirred at 60° C. for 18 hours. A further 0.1 parts of sodium was dissolved in 10 parts of 2,2,2-trifluoroethanol and added to the reaction mixture. Stirring at 60° C. was continued for a further 24 hours then the reaction mixture was cooled and evaporated in vacuo. The residue was partitioned between ethyl acetate and water. The organic layer was separated, washed with water, dried (MgSO4) and evaporated. The crude product was purified by chromatography on silica (Merck Kieselgel 60 using a 50:50 mixture of ether and 40°-60° petroleum ether as eluent followed by recrystallisation from a mixture of 60°-80° petroleum ether and ethyl acetate to give 2-amino-4-chloromethyl-6-(2,2,2-trifluoroethoxy)pyrimidine m.p. 77°-78° C.

出典