Ammonium Chloride → (+/-)-(4R*,5R*)-5-[(1S*)-hydroxy(5-methyl(2-thienyl))methyl]-1-methyl-4-phenylpyrrolidin-2-one

Participants

Reaction Steps

A portion (1 mL) of a solution of 2-bromo-5-methylthiophene (0.56 mL, 5.5 mmol) in THF (20 mL) was added to Mg turnings (135 mg, 5.5 mmol). The mixture was gently heated until the magnesium started to be consumed. The remaining thiophene solution was added in 1 mL increments to maintain a constant gentle reflux. After the addition was complete, the solution was heated at the reflux temperature for 3 min, then was allowed to cool to room temperature. To a −78° C. solution of (±)-(4R*,5R*)-5-formyl-1-methyl-4-phenylpyrrolidin-2-one (Intermediate Z, 190 mg, 1 mmol) in THF (7.5 mL) was slowly added the freshly prepared Grignard reagent and the reaction mixture was allowed to warm to room temperature. After 2 h a saturated NH4Cl solution was added and the mixture was extracted with EtOAc, dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (100% EtOAc) to give (±)-(4R*,5R*)-5-[(1S*)-hydroxy(5-methyl(2-thienyl))methyl]-1-methyl-4-phenylpyrrolidin-2-one (156 mg, 52%) as a white powder: mp 185-188° C.

Provenance & Evidence