吡咯经苯甲酰氯酰化、与1,2- 二氯乙烷N- 烃化、丙二酸二乙酯C- 烃化、环合反应、水解反应和脱羧反应得到5- 苯甲酰基-1,2- 二氢-3H- 吡咯并[1,2-a] 吡咯-1- 羧酸(7)，再与氨丁三醇成盐得酮咯酸氨丁三醇(1)，纯度≥ 99.5％，总收率51％ ( 以吡咯计)。在N- 烃化和C- 烃化时加入DMF，反应快速、彻底，收率提高；制备7 时，加浓盐酸调至pH 2 脱羧，用甲醇- 水替代二氯甲烷- 环己烷进行纯化。最后在无水乙醇中成盐得1，操作简便。
Abstract
5-Benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid(7) was obtained from pyrrole by benzoylation with benzoyl chloride, N-alkylation with 1,2-dichloroethane, C-alkylation with diethyl malonate, cyclization, hydrolysis and decarboxylation. Then ketorolac tromethamine(1) was obtained by salt formation with a purity≥99.5％ and a total yield of 51％ (based on pyrrole). DMF was added into the reaction systems in the N-alkylation and C-alkylation steps, so that the reaction was faster and the yield was increased. The decarboxylation was carried out at pH 2 adjusted by concentrated HCl and methanol-water was used instead of dichloromethane-cyclohexane to purify compound 7. Finally, 1 was obtained by salt formation in anhydrous ethanol. The improved process was easy to operate.
关键词
酮咯酸氨丁三醇 /
镇痛药 /
非甾体抗炎药 /
合成工艺
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Key words
ketorolac tromethamine /
analgesic /
nonsteroidal antiinflammatory drug /
synthetic process
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参考文献
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