Ammonium Chloride → (4R,5R)-5-((S)-(5-(4-fluorophenyl)thiophen-2-yl)(hydroxy)methyl)-1-methyl-4-phenylpyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a −65° C. solution of 2-(4-fluorophenyl)thiophene (Intermediate O; 853.6 mg, 5.79 mmol) in THF (5 mL) was added a solution of n-BuLi (2.5M in hexane, 1.8 mL, 4.5 mmol). The reaction mixture was allowed to warm to −20° C. over the period of 1 h. After cooling down to −65° C. again, a solution of (±)-(4R*,5R*)-5-formyl-1-methyl-4-phenylpyrrolidin-2-one (Intermediate Z, 6.38 mmol) in THF (5 mL) was added. The reaction mixture was stirred for 1 h, while allowing to warm to −20° C., then treated with a saturated NH4Cl solution (15 mL). The resulting mixture was extracted with EtOAc (4×15 mL), dried (MgSO4) and concentrated under reduced pressure. The crude brown solid was triturated (Et2O/hex) to give (±)-(4R*,5R*)-5-{(1S*) [5-(4-fluorophenyl)(2-thienyl)]hydroxymethyl}-1-methyl-4-phenylpyrrolidin-2-one (330 mg, 24%) as a fine brown solid: mp 110° C. (dec); TLC (EtOAc) Rf 0.52.

Provenance & Evidence