Naphthalene → (4R)-4-[4-chloro-2-(phenylcarbonyl)phenyl]pyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a mixture of lithium wire (30 mg, 4.28 mmol), naphthalene (52 mg, 0.66 mmol), and MnBr2 (0.64 g, 2.08 mmol) was cannulated anhydrous tetrahydrofuran (THF) under a nitrogen atmosphere. The mixture was stirred for 2 h at room temperature before (4R)-4-(2-bromo-4-chlorophenyl)pyrrolidin-2-one in anhydrous THF (2 mL) was added dropwise. After stirring for 1 h, the reaction mixture was cooled to 0° C. and 1,2-dibromoethane (0.3 mL, 1.89 mmol) was added. The reaction mixture was warmed to room temperature before a solution of CuI (11.4 mg, 0.06 mmol) in THF (1 mL) was introduced via cannulation. The mixture was then stirred for 5 min and benzoyl chloride (0.1 mL, 0.66 mmol) was added. The reaction mixture was stirred overnight at room temperature. The reaction was diluted with water (1.5 mL) and extracted with ethyl acetate (3×5 mL). The combined organic phases were washed with brine and dried over MgSO4. The solvent was removed in vacuo to provide (4R)-4-[4-chloro-2-(phenylcarbonyl)phenyl]pyrrolidin-2-one. The crude residue was treated with a 6N HCl aq. solution and heated overnight. The crude residue was purified by HPLC to afford the title compound (11). 1H-NMR (400 MHz, CD3OD): δ 2.71-2.87 (m, 2H), 3.44-3.59 (m, 3H), 7.27 (s, 3H), 7.37-7.41 (m, 2H), 7.46-7.48 (m, 1H), 7.66-7.68 (m, 2H); MS (ESI) m/z 318.09 (M+H)+.

Provenance & Evidence