反应详情

温度

22.5 °C

21.0 g (0.1 mol) 4-(4-fluor-benzoil)-butyric acid (II) was weighed into a 500 ml round-bottom flask and suspended in 210 ml dichloro methane. During continuous stirring 28 ml (31.2 g, 0.5 mol) ethylene-glycol, 32 ml (31.04 g, 0.3 mol) trimethyl-ortho-formiate, and 0.5 ml conc. sulphuric acid is added dropwise into the suspension. The reaction mixture was stirred at 20-25° C. for 3-6 h. The reaction was analytically controlled by thin-layer chromatography. When the ketone came to an end, as its spot disappeared by thin-layer chromatography, the reaction was stopped with adding 5 g solid NaHCO3. The suspension was stirred for 05 min., then the solvent is removed by evaporation, and the residue is solved in 150 ml methanol. This solution was cooled in an icy water-bath, and during the cooling 100 ml 10% NaOH solution was added. The flask was closed and the turbid mixture was stirred at 20-25° C. for about 1 h. The hydrolysis was analytically controlled by thin-layer chromatography. When the ester came to an end, as its spot disappeared by thin-layer chromatography, the methanol was removed by vacuum evaporation, and during intensive cooling in an icy water-bath, 350 ml 10% citric acid solution was added to the residue to achieve an acidic pH-value between 3-4. The precipitated product was extracted with 200 ml ethyl acetate. The aqueous phase was extracted twice with 50-50 ml ethyl acetate, and then the united organic phase was washed to neutral with 5×50 ml water. The ethyl acetatic solution was dried on anhydrous Na2SO4, the desiccant was filtered out, and the filtrate was evaporated in vacuum. The evaporating residue is crystallized with addition of 50 ml n-hexane at 0° C. The crystalline material of (IV) is isolated by filtration, and is dried.

1. additionis added dropwise into the suspension
2. stirringThe suspension was stirred for 05 min
3. custom, then the solvent is removed by evaporation
4. temperatureThis solution was cooled in an icy water-bath
5. additionduring the cooling 100 ml 10% NaOH solution was added
6. customThe flask was closed
7. stirringthe turbid mixture was stirred at 20-25° C. for about 1 h
8. customthe methanol was removed by vacuum evaporation
9. temperatureduring intensive cooling in an icy water-bath
10. addition350 ml 10% citric acid solution was added to the residue
11. extractionThe precipitated product was extracted with 200 ml ethyl acetate
12. extractionThe aqueous phase was extracted twice with 50-50 ml ethyl acetate
13. washthe united organic phase was washed to neutral with 5×50 ml water
14. dry with materialThe ethyl acetatic solution was dried on anhydrous Na2SO4
15. filtrationthe desiccant was filtered out
16. customthe filtrate was evaporated in vacuum
17. customThe evaporating residue is crystallized with addition of 50 ml n-hexane at 0° C