反应详情

To a suspension of methyl(triphenyl)phosphonium bromide (248 g, 0.69 mol) in anhydrous toluene (1 L) was added sodium hexamethyldisilazide (258 ml, 0.69 mmol) at 0° C., after addition was completed, the reaction mixture was warmed to room temperature, and stirred at room temperature for 1 hour, then cooled to 0° C. and the solution of (S)-4-oxo-piperidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester (intermediate 14, 210 g, 0.63 mol) in anhydrous toluene (0.5 L) was added. The resulting mixture was warmed to room temperature, and stirred at room temperature for 1 hour, added water (500 ml), extracted with ethyl acetate. The combined organic extracts were dried (Na2SO4), filtered and evaporated to obtain a crude that was purified by silica gel chromatography (petroleum ether/ethyl acetate from 10/1 to 5/1). (S)-4-Methylene-piperidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester was obtained as colourless oil (120 g), yield:57.4%.

1. additionafter addition
2. temperaturecooled to 0° C.
3. temperatureThe resulting mixture was warmed to room temperature
4. stirringstirred at room temperature for 1 hour
5. extractionextracted with ethyl acetate
6. dry with materialThe combined organic extracts were dried (Na2SO4)
7. filtrationfiltered
8. customevaporated
9. customto obtain a crude that
10. customwas purified by silica gel chromatography (petroleum ether/ethyl acetate from 10/1 to 5/1)