反应详情

温度

50 °C

6 g of ethyl 2-(2-ethoxyethyl)oxymalonate (24.65 mmoles) are added to a solution of sodium ethoxide in EtOH (15 ml, prepared by dissolution of 0.65 g, 0.028 moles metal Na) under stirring and nitrogen atmosphere. Stirring is continued for 1 h at room temperature, then a solution of 3-trityloxy-1-propyl-bromide (9.4 g, 24.7 mmoles) in EtOH (20 ml) is added dropwise. The reaction mixture is heated at 50° C. and kept at this temperature overnight. When the reaction is completed, the solvent is evaporated off under vacuum and the residue is partitioned between water and AcOEt. The aqueous phase is re-extracted with AcOEt (2×50 ml), the combined organic phases are washed to neutrality with a 5% NaH2PO4 aqueous solution, then with water, and finally dried over sodium sulfate. After evaporation of solvent, the resulting solution of crude ethyl 5-trityloxy-2-ethoxycarbonyl-2-[(2-ethoxy)ethyloxy]-pentanoate in EtOH is treated with 0.3 g of p-toluenesulfonic.H2O acid and kept for 12 h at room temperature. After evaporation of solvent, the residue is dissolved in dichloromethane (15 ml) and the organic phase is washed with 2×5 of 5% aqueous NaHCO3, then with water to neutrality, dried over Na2SO4, the solvent is evaporated off and the residue is purified on a silica gel column (eluent CHCl3 /MeOH 98:1.5), to obtain 6.42 g of ethyl 5-hydroxy-2-[(2-ethoxy)ethyloxy]-2-ethoxycarbonyl-pentanoate.

1. stirringStirring
2. customkept at this temperature overnight
3. customthe solvent is evaporated off under vacuum
4. customthe residue is partitioned between water and AcOEt
5. extractionThe aqueous phase is re-extracted with AcOEt (2×50 ml)
6. washthe combined organic phases are washed to neutrality with a 5% NaH2PO4 aqueous solution
7. dry with materialwith water, and finally dried over sodium sulfate
8. customAfter evaporation of solvent
9. additionthe resulting solution of crude ethyl 5-trityloxy-2-ethoxycarbonyl-2-[(2-ethoxy)ethyloxy]-pentanoate in EtOH is treated with 0.3 g of p-toluenesulfonic
10. waitH2O acid and kept for 12 h at room temperature
11. customAfter evaporation of solvent
12. dissolutionthe residue is dissolved in dichloromethane (15 ml)
13. washthe organic phase is washed with 2×5 of 5% aqueous NaHCO3
14. dry with materialwith water to neutrality, dried over Na2SO4
15. customthe solvent is evaporated off
16. customthe residue is purified on a silica gel column (eluent CHCl3 /MeOH 98:1.5)