摘要
以金刚烷甲酸(1)为起始原料,经过酰化,取代,脱羧三步反应一锅法制得金刚烷甲基酮(2),然后氧化甲基得到1-金刚烷基乙醛酸(3),将3与盐酸羟氨反应得到1-金刚烷乙醛酸肟(4),还原4并用BOC酸酐保护氨基得到N-叔丁氧羰基-1-金刚烷基甘氨酸(5),最后经高锰酸钾氧化得到DPP-IV抑制剂沙格列汀中间体N-叔丁氧羰基-3-羟基-1-金刚烷基甘氨酸(6),总收率28%。
1-Adamantylmethylketone(2) was synthesized using 1-adamantane carboxylic acid(1) as the starting material,through acylation,substitution,decarboxylation to afford. The compounds 2 was converted into 2-(1-adamantyl)-2-oxoacetic acid(3)by oxi-dation with potassium permanganate. Compound 3 reacted with hydroxylamine hydrochloride to give the 1-adamantly-2-hydroxyimino acetic acid(4),and then reduction of oxime 4 and protection of amino with Boc2O to afford N-Boc-adamantylglycine(5),hydroxyl-ation of the adamantane ring using KMnO4 afforded dipeptidyl peptidase IV( DPP-IV) inhibitor saxagliptin intermediate N-Boc-3-hydroxyadamantylglycine(6)and the overall yield is about 28%.
出处
《化学研究与应用》
CAS
CSCD
北大核心
2014年第4期527-531,共5页
Chemical Research and Application
基金
重庆市自然科学基金项目(CSTC 2006BB5286)资助