2-[6,7-二氢-1H-茚并[5,4-b]呋喃-8(2H)-基亚基]乙酸乙酯的合成

Synthesis of Ethyl 2-[6,7-dihydro-1H-indeno[5,4-b]furan-8(2H)-ylidene]acetate

3-碘苯酚与1,2-二溴乙烷反应得3-碘-1-(2-溴代乙氧基)苯(4);另用丙二醇经二氧化锰氧化、与乙氧甲酰基亚甲基三苯膦经Wittig反应、羟基溴代得5-溴-2-戊烯酸乙酯(7)。用4和7在乙酸钯/三苯膦/降冰片烯作用下,与丙烯酸乙酯经C-H活化和分子内Heck反应得雷美替胺关键中间体2-[6,7-二氢-1H-茚并[5,4-b]呋喃-8(2H)-亚基]乙酸乙酯,总收率约51%。

1-（2-Bromoethoxy）-3-iodobenzene （4） was prepared from 3-iodophenol and 1,2-dibromoethane. And ethyl 5-brome-2-penenoate （7） was prepared from propylene glycol by reduction with MnO2, Wittig reaction with ethyl （triphenylphosphoranylidene） acetate and bromonation. Ethyl 2- [6,7-dihydro- 1H-indeno [5,4-b] furan-8 （2H） - ylidene] acetate, the intermediate of ramelteon, was synthesized from 4 and 7 in the presence of palladium acetate/ triphenylphosphine/norbomene with an overall yield of about 51%.