反应详情

A mixture of 25 g of ethyl (4-methoxy-phenyl)-acetate, 27.4 g of 1-bromo-4-cyano-3-fluoro-benzene and 20 mL of N-methyl-pyrrolidin-2-one is slowly added to 31.4 g of potassium tert butoxide in 130 mL of N-methyl-pyrrolidin-2-one keeping the temperature below 10° C. After stirring for 1 hour at room temperature, 100 mL of methanol and 137 mL of 1 M aqueous sodium hydroxide are added and the mixture is stirred overnight at room temperature. The methanol fraction is evaporated, the residue is basified with 1 M aqueous sodium hydroxide and extracted with tert butyl-methyl ether. The aqueous phase is acidified with 4 M hydrochloric acid and extracted with ethyl acetate several times. The combined ethyl acetate extracts are evaporated and the residue together with 120 mL of N,N-dimethyl formamide and 24.9 g of potassium carbonate heated at 100° C. for 1 hour. The reaction mixture is diluted with aqueous sodium bicarbonate and extracted several times with ethyl acetate. The combined extracts are evaporated and the residue crystallized from methanol.

1. stirringthe mixture is stirred overnight at room temperature
2. customThe methanol fraction is evaporated
3. extractionextracted with tert butyl-methyl ether
4. extractionextracted with ethyl acetate several times
5. customThe combined ethyl acetate extracts are evaporated
6. temperaturethe residue together with 120 mL of N,N-dimethyl formamide and 24.9 g of potassium carbonate heated at 100° C. for 1 hour
7. additionThe reaction mixture is diluted with aqueous sodium bicarbonate
8. extractionextracted several times with ethyl acetate
9. customThe combined extracts are evaporated
10. customthe residue crystallized from methanol