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

Participants

Reaction Steps

Intermediate Y 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 1 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 product, (±)-(4R*,5R*)-5[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]-1-methyl-4-[4-tert-butyldimethylsilyloxy)phenyl]pyrrolidin-2-one (0.050 g, 0.10 mmol), was dissolved in THF (1 mL) under Ar, a solution of TBAF (1M in THF, 0.11 mL, 0.11 mmol) was added, and the resulting solution was stirred for 4 min. The reaction was treated with water and a saturated NH4Cl solution, then extracted with EtOAc. The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by flash chromatography (EtOAc) to yield (±)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-hydroxy-phenyl)-1-methylpyrrolidin-2-one (31 mg, 82%) as a white powder: mp 248-249° C.; TLC (EtOAc) Rf 0.37.

Provenance & Evidence