2-Phenylthiophene → (+/-)-(4R*,5R*)-5-[(1S*)Hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-(ethoxycarbonyl)-phenyl)-1-methylpyrrolidin-2-one

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Reaction Steps

Intermediate V was reduced with lithium triethylborohydride using the method described as Method 2 in the preparation of Intermediate T. The resulting alcohol was then subjected to Swern oxidation using the procedure described as Method I in the preparation of Intermediate Z, followed by a reaction of the resulting aldehyde with 2-phenylthiophene and n-BuLi in a manner analogous to that of Example 3a. The resulting compound, (±)-(4R*,5R*)-5-[(1S*)hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-iodophenyl)-1-methylpyrrolidin-2-one (0.100 g, 0.205 mmol), Et3N (0.1 mL) and Pd(OAC)2 (ca 10 mg) were stirred in EtOH (1 mL) under an atmosphere of carbon monoxide at 60° C. for 36 h. The resulting mixture was concentrated onto silica and the product isolated by flash chromatography (EtOAc) to yield (±)-(4R*,5R*)-5-[(1S*)hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-(ethoxycarbonyl)phenyl)-1-methyl-pyrrolidin-2-one (60 mg, 67%) as an orange solid: mp 177-179° C.; TLC (EtOAc) Rf 0.62.

Provenance & Evidence