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

Participants

Reaction Steps

A mixture of (±)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]-1-methyl-4-[4-(methylamino)phenyl]pyrrolidin-2-one (Example 18, 70 mg, 0.18 mmol), methyl iodide (26 mg, 0.18 mmol) and potassium carbonate (49 mg, 0.36 mmol) in acetonitrile (1 mL) was stirred for 3 h. More methyl iodide (0.26 mg, 0.18 mmol) was added and the mixture was heated at the reflux temperature for 2 h. The reaction mixture was treated with sodium methoxide (20 mg, 0.36 mmol) and methanol (1 mL) and heated at the reflux temperature overnight. The resulting mixture was diluted with water (10 mL) and extracted with EtOAc (2×10 mL). The combined organic layers were washed with a saturated NaCl solution, dried (Na2SO4) and concentrated under reduced pressure. The crude product was purified by flash chromatography (EtOAc) to give a colorless oil, which was sequentially triturated with EtOAc, Et2O and hexane to provide (±)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]4-[4-(dimethylamino)phenyl]-1-methylpyrrolidin-2-one (10 mg, 14%) as an off-white solid: TLC (EtOAc) Rf 0.40; HPLC ES-MS m/z (rel abundance) 407 (MH+, 100%).

Provenance & Evidence