反应详情

温度

60 °C

A solution of dry sodium (RS)-4-hydroxy-4-(2-methylphenyl)butanoate (0.18 g) in dry tetrahydrofuran (50 mL) is treated with sodium hydride and stirred at 60° C. for 15 minutes. tert-Butyl 3-[(4-cyano-3-fluoro-phenoxymethyl)phenyl]propionate (0.2 g) is added and the mixture heated at reflux for 4 hours. After standing at room temperature for 18 hours the reaction mixture is filtered. Ethyl acetate (50 mL) and 1 N hydrochloric acid (50 mL) are added to the filtrate and the organic phase is separated. The organic phase is washed with water (10 mL), dried over magnesium sulphate, evaporated and the residue purified by flash chromatography on silica eluting with a mixture of dichloromethane and methanol (95:5 v/v). Fractions homogeneous in the required product are combined and evaporated. The residue is dissolved in ether and the solution washed with 1% sodium bicarbonate solution, 0.5 N hydrochloric acid, water, dried over magnesium sulphate and evaporated. The resulting colourless gum is crystallised from a mixture of cyclohexane and ethyl acetate to give (RS)-4-{5-[3-(2-carboxyethyl)benzyloxy]-2-cyano-phenoxy}-4-(2-methylphenyl)butanoic acid (0.12 g) m.p. 136-137° C. [Elemental analysis:- C,71.4; H,6.23; N,2.91%. Calculated:- C,71.0; H,5.75; N,2.96%].

1. temperaturethe mixture heated
2. temperatureat reflux for 4 hours
3. waitAfter standing at room temperature for 18 hours
4. filtrationthe reaction mixture is filtered
5. additionEthyl acetate (50 mL) and 1 N hydrochloric acid (50 mL) are added to the filtrate
6. customthe organic phase is separated
7. washThe organic phase is washed with water (10 mL)
8. dry with materialdried over magnesium sulphate
9. customevaporated
10. customthe residue purified by flash chromatography on silica eluting with a mixture of dichloromethane and methanol (95:5 v/v)
11. customevaporated
12. dissolutionThe residue is dissolved in ether
13. washthe solution washed with 1% sodium bicarbonate solution, 0.5 N hydrochloric acid, water
14. dry with materialdried over magnesium sulphate
15. customevaporated
16. customThe resulting colourless gum is crystallised from a mixture of cyclohexane and ethyl acetate