What is 1,2,6,7-Tetrahydro-8H-indeno[5,4-b]furan-8-one?
1,2,6,7-Tetrahydro-8H-indeno[5,4-b]furan-8-one is a key intermediate for preparation of ramelteon, a MT1 and MT2 melatonin receptor selective agonist.

Brief introduction of ramelteon
Previously, sleep agents bind to GABAA receptors which are associated with anxiolytic, myorelaxant, and amnesic effects, such as with drugs like zolpidem, eszopiclone, and zaleplon. As the first in a new class of sleep agents, Ramelteon selectively binds to the MT1 and MT2 receptors in the suprachiasmatic nucleus (SCN). It was developed by Takeda Pharmaceuticals North America with the trade name Rozerem, and was approved by the U.S. Food and Drug Administration (FDA) on July 4th, 2005 for long-term use. It can be used for insomnia, delayed sleep onset in particular. There is no proof showing that Ramelteon produces dependence and any potential for abuse. What's more, while there is withdrawal and rebound insomnia typically with GABA modulators, it is not shown in ramelteon. Ramelteon can also be used for the treatment of Delayed sleep phase syndrome. Ramelteon was proven by practice to be associated with a lower risk of delirium (3% vs 32%; P = .003). According to Chakraborti, D; Tampi, D. J.; Tampi, R. R. (2014) ( "Melatonin and Melatonin Agonist for Delirium in the Elderly Patients". American journal of Alzheimer's disease and other dementias), "ramelteon was found to be beneficial in preventing delirium in medically ill individuals when compared to placebo."

The way to synthetize 1,2,6,7-Tetrahydro-8H-indeno[5,4-b]furan-8-one
The key intermediate for synthetizing 1,2,6,7-Tetrahydro-8H-indeno[5,4-b]furan-8-one is 3-(2,3-dihydrobenzofuran-5-yl)propanoic acid. This intermediate is prepared by condensation of p-bromophenol with bromoacetaldehyde diethyl acetal in the presence of K2CO3 and Friedel-Crafts reaction to give 5-bromobenzofuran, which is subsequently subjected to Heck coupling reaction with methyl acrylate in the presence of palladium acetate, then catalytic hydrogenation and hydrolysis in one pot reaction. After that, 1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-one was synthesized from 3-(2,3-dihydrobenzo- furan-5-yl)propanoic acid through bromination, Friedel-Crafts acylation and catalytic hydrogenolysis debromination. The overall yield is around 49.9%. The structures of intermediates and final product are determined by 1H NMR, 13C NMR and HRMS techniques. The advantages of this method are easily available starting materials, simply conducted procedures, relatively high yield and easy purification, therefore is feasible for scale-up production.