摘要
以N-甲基吡咯为起始原料,与草酰氯单乙酯缩合成双羰基酯,再碱水解为羧酸盐,经黄鸣龙反应还原、酸化得到1-甲基吡咯-2-乙酸,后者与氯甲酸甲酯的缩合物与对甲基苯甲酰氯对接生成中间体,在甲醇中回流得到[1-甲基-5-(4-甲基-苯甲酰基)-1H-吡咯-2-基]-乙酸甲酯,后者经碱水解然后酸化精制得到目标产品托美汀。五步反应以N-甲基吡咯计总收率为60%,托美汀含量高于99%,具有较大的产业化生产优势。
In the presence of alkaline liquor, the dicarbonyl ester obtained from condensation reaction of ethyl oxalyl monochloride and N -Methylpyrrole is hydrolyzed to carboxylate which is reduced to I - methyl- 1H -pyrrole -2 -acetic acid according to Kishner- Wolff- Huang reduction reaction following by aciding the reduction resultant. The latter is condensed with methyl chloroformate following by reacting with p - toluoylchloride. The intermediate obtained is refluxed in methanol, and [ 1 - methyl - 5 - （4 - methyl - benzoyl） - 1H - pyrrole - 2 - yl] - acetic acid methyl ester is obtained. The latter is hydrolyzed in the presence of alkaline liquor following by aciding and purified. The destination product tolmetin is achieved by the total yield 60% ,the purity is above 99%, and the procedure is practical.
出处
《山东化工》
CAS
2013年第11期33-36,共4页
Shandong Chemical Industry
关键词
托美汀
N-甲基吡咯
1-甲基吡咯-2-乙酸
非甾体抗炎药
黄鸣龙反应
tolmetin
N - methyl pyrrole
1 - methyl - 1H - pyrrole - 2 - acetic acid
non - steroidal anti - inflammatory drug
Kishner - Wolff - Huang reduction reaction
