反应详情

温度

-75 °C

A solution of diisopropylamine (120.6 mL, 0.86 mol) (Aldrich) in tetrahyrofuran (370 mL) was cooled to −30° C. n-Butyllithium (2.5 M in hexanes, 344.2 mL, 0.86 mol) (Aldrich) was added drop wise at such a rate that the reaction mixture temperature was kept between −30 to 0° C. The reaction mixture was then cooled to −75° C. in a dry ice-acetone bath. A solution of ethyl butyrate (100 g, 0.86 mol) (Aldrich) in tetrahydrofuran (170 mL) was added drop wise over 28 minutes and keeping the reaction temperature between −75 to −70° C. The mixture was stirred at the same temperature for an additional 30 minutes. Ethyl formate (125 mL, 1.55 mol) (Aldrich) was then added to this mixture over 25 minutes and maintaining the temperature between −75 to −70° C. The resultant mixture was allowed to warm to room temperature and stirred at room temperature for 3 hours. With external cooling in a cold water bath to keep the reaction temperature below 30° C. acetic acid (98.55 mL, 1.72 mol) was added, followed by water (430 mL) and dichloromethane (200 mL). After separating the layers, the organic layer was washed with water (300 mL). The combined water layer was extracted with dichloromethane (200 mL). The combined organic layer was washed with aqueous sodium bicarbonate solution (200 mL). The basic aqueous solution was extracted with dichloromethane (100 mL). All organic layers were then combined, dried over sodium sulfate over night, filtered and distilled to remove solvent leaving about 180 mL. (Some of the product was distilled over with tetrahydrofuran.) The residue was distilled at 65–81° C. (23 mm Hg). The fraction distilling over at 70–81° C. (23 mm Hg) gave ethyl 2-formylbutyrate. (Yield 68.35 g, 55.1%).

1. additionwas added drop wise at such a rate that the reaction mixture temperature
2. customwas kept between −30 to 0° C
3. custombetween −75 to −70° C
4. temperaturemaintaining the temperature between −75 to −70° C
5. temperatureto warm to room temperature
6. stirringstirred at room temperature for 3 hours
7. temperatureWith external cooling in a cold water bath
8. additionwas added
9. customAfter separating the layers
10. washthe organic layer was washed with water (300 mL)
11. extractionThe combined water layer was extracted with dichloromethane (200 mL)
12. washThe combined organic layer was washed with aqueous sodium bicarbonate solution (200 mL)
13. extractionThe basic aqueous solution was extracted with dichloromethane (100 mL)
14. dry with materialdried over sodium sulfate over night
15. filtrationfiltered
16. distillationdistilled
17. customto remove solvent
18. customleaving about 180 mL
19. distillation(Some of the product was distilled over with tetrahydrofuran
20. distillation) The residue was distilled at 65–81° C. (23 mm Hg)
21. distillationThe fraction distilling over at 70–81° C. (23 mm Hg)