反应详情

To a solution of (S)-4-methylene-piperidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester (intermediate 15 prepared by Method A, 120 g, 0.36 mol) in anhydrous THF (1 L) was added diazomethane in ether (500 ml) [which was prepared from methyl-3-nitro-1-nitroxoguanide (213 g) in 40% KOH (1 L)] at −25° C. to −35° C. slowly under the protection of nitrogen and warmed to room temperature slowly (about 4 hours) and stirred at room temperature for 10 hours. The mixture is filtered and the liquid phase was evaporated to obtain a crude that was purified by silica gel chromatography (petroleum ether/ethyl acetate from 10/1 to 5/1). (S)-6-Aza-spiro[2.5]octane-5,6-dicarboxylic acid 5-benzyl ester 6-tert-butyl ester was obtained as colourless oil (110 g), yield:88%.

1. filtrationThe mixture is filtered
2. customthe liquid phase was evaporated
3. customto obtain a crude that
4. customwas purified by silica gel chromatography (petroleum ether/ethyl acetate from 10/1 to 5/1)