Dichloromethane → (+/-)-(4R*,5R*)-5-{(1 S *)[5-(3-chloro-4-fluorophenyl) (2-thienyl)]hydroxymethyl}-1-methyl-4-phenylpyrrolidin-2-one

Participants

Reaction Steps

To a solution of (±)-(4R*,5R*)-5-[(1S*)(5-bromo(2-thienyl))hydroxymethyl]-1-methyl-4-phenylpyrrolidin-2-one (300 mg, 0.82 mmol) in 1,2-dimethoxyethane (2.8 mL) was added 3-chloro-4-fluorobenzeneboronic acid (85.9 mg, 1.07 mmol), followed by a 1M Na2CO3 solution (2.2 mL). A catalytic amount of Pd(PPh3)4 was added and the reaction mixture was heated at the reflux temperature for 3 h, then allowed to cool to room temperature and poured onto a mixture of ice and CH2Cl2. The resulting mixture was extracted with CH2Cl2, dried (MgSO4) and concentrated under reduced pressure. The crude product was triturated (Et2O/ cyclohexane) to give (±)-(4R*,5R*)-5-{(1S*)[5-(3-chloro-4-fluorophenyl)(2-thienyl)]hydroxymethyl}-1-methyl-4-phenylpyrrolidin-2-one (235 mg, 69%): mp 194° C.; TLC (EtOAc) Rf 0.47

Provenance & Evidence