合成路线1

The reaction of 2,3-dihydrobenzofuran (I) with DMF (II) and POCl3 gives 2,3-dihydrobenzofuran-5-carbaldehyde (III), which is condensed with the phosphonate (IV) by means of t-BuONa in toluene to yield the acrylate (V). The reduction of (V) with H2 over Pd/C in AcOH affords the corresponding propionate (VI), which is brominated with Br2 in AcOH to provide the dibromo derivative (VII). The hydrolysis of the ester group of (VII) in acidic medium gives the expected propionic acid derivative (VIII), which is treated with SOCl2 in dichloromethane to yield the propionyl chloride (IX). The cyclization of (IX) by means of AlCl3 in dichloromethane affords the 4,5-dibromo-2,6,7,8-tetrahydro-1H-indeno[5,4-b]furan-8-one (X), which is submitted to an hydrogenolytic debromination with H2 over Pd/C in methanol to provide the 2,6,7,8-tetrahydro-1H-indeno[5,4-b]furan-8-one (XI). The Wittig condensation of (XI) with phosphonate (XII) by means of NaOMe in toluene gives 2-(2,6,7,8-tetrahydro-1H-indeno[5,4-b]furan-8-ylidene)acetonitrile (XIII), which is reduced with H2 and Raney-Co in toluene/MeOH to yield 2-(2,6,7,8-tetrahydro-1H-indeno[5,4-b]furan-8-ylidene)ethylamine (XIV). The asymmetric reduction of (XIV) with H2 and a chiral Ru catalyst in toluene/MeOH affords the 2-(2,6,7,8-tetrahydro-1H-indeno[5,4-b]furan-8(S)-yl)ethylamine (XV), which is finally acylated with propionyl chloride (XVI) and NaOH in aq. THF to provide the target chiral propionamide.

合成路线2