(R)-N-methoxy-1-((R)-1-(4-methoxyphenyl)ethyl)-N-methyl-5-oxopyrrolidine-3-carboxamide → (R)-1-((R)-1-(4-Methoxyphenyl)ethyl)-4-propionylpyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

Into a 500-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of N-methoxy-1-[(1R)-1-(4-methoxyphenyl)ethyl]-N-methyl-5-oxopyrrolidine-3-carboxamide 1.02 (20 g, 65.28 mmol, 1.00 equiv) in tetrahydrofuran (200 mL), followed by the addition of bromo(ethyl)magnesium in THF (1 M) (44 mL) dropwise with stirring at −10° C. The resulting solution was stirred at −10° C. for 2 h, quenched by the addition of 200 mL of water/ice and extracted with 3×500 mL of ethyl acetate. The organic layers were combined, washed with 2×500 mL of hydrogen chloride (1 M) and 3×500 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column eluting with ethyl acetate: petroleum ether (1:5-1:1) to afford (R)-1-((R)-1-(4-methoxyphenyl)ethyl)-4-propionylpyrrolidin-2-one 1.22.

Provenance & Evidence