反应详情

250 ml of THF are added to a stirred suspension of 300 mmol of sodium hydride, which has been washed with n-pentane, and 280 mmol of 3-oxobutylphosphonic acid diethyl ester (1a) are added dropwise at room temperature. After 2 hours' stirring at constant temperature, the reaction mixture is cooled with an ice/common salt mixture and 1.3 equivalents of n-BuLi are added dropwise. After a further 2 hours' stirring at 0° C., 310 mmol of benzyl bromide (dissolved in 50 ml of THF) are slowly added. The mixture is allowed to rise to room temperature, stirred for a further 3 hours and combined with 20 ml of 1 molar HCl. The reaction solution is poured into iced water, extracted three times with 100 ml portions of chloroform and the combined organic phases are washed with saturated common salt solution. Purification of 1b performed chromatographically on silica gel with methylene chloride and ethyl acetate as mobile solvent. (Reaction conditions, c.f.: B. Resul, J. Stjernschantz, K. No, C. Liljebris, G. Selén, M. Astin, M. Karlsson, L. Z. Bito J. Med. Chem. 1993, 36, 243-248)

1. additionare added dropwise at room temperature
2. additionare added dropwise
3. stirringAfter a further 2 hours' stirring at 0° C.
4. customto rise to room temperature
5. stirringstirred for a further 3 hours
6. extractionextracted three times with 100 ml portions of chloroform
7. washthe combined organic phases are washed with saturated common salt solution
8. customPurification of 1b
9. custom(Reaction conditions