Synthesis of (s)-n-[2-(1,6,7,8-tetrahydro-2h-indeno-[5,4-b]furan-8-yl)ethyl]propionamide

A process for preparing a compound of formula VII comprising the steps of:

• a.) providing a compound of formula VI:
• wherein EVVG means an electron withdrawing group;
• and
• b.) performing asymmetric reduction reaction of the compound of formula VI in the presence of metal-(optically active posphine)-complex catalyst, wherein metal is preferably selected from the group consisting of Cu, Co, Ni, Rh, Ru, Pd and Ir, to give the compound of formula VII:

A process for preparing ramelteon (VIIIa) comprising the steps of:

• a.) preparing the compound of formula VIIa by a process comprising subjecting a compound of formula VIa to asymmetric reduction in the presence of the copper-(optically active phosphine)-complex catalyst and hydride source, wherein said copper-(optically active phosphine)-complex catalyst is prepared from copper and ferrocenyl phosphines selected from the compounds having formula:
• wherein R1 and R2 are independently selected from the group consisting of independently substituted or unsubstituted alkyl, cycloalkyl, aryl heteroaryl, arylalkyl and heteroarylalkyl group;
• and
• b.) reacting a compound of formula VIIa with hydrogen and propionic anhydride in the presence of catalyst, wherein said catalyst is Raney-Ni, to yield a compound of formula VIIIa