Sodium borohydride → (4R)-4-(1-Hydroxypropyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

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Reaction Steps

Into a 250-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed (4R)-1-[(1R)-1-(4-methoxyphenyl)ethyl]-4-propanoylpyrrolidin-2-one 1.22 (6 g, 21.79 mmol, 1.00 equiv), ethanol (60 mL), followed by the addition of NaBH4 (1.85 g, 48.68 mmol, 2.50 equiv) in several batches with stifling at 0° C. The resulting solution was stirred at room temperature for 2 h, quenched by the addition of 100 mL of water/ice, extracted with 3×200 mL of ethyl acetate. The organic layers were combined, washed with 2×200 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was washed with 1×100 mL of ether and the solids were collected by filtration to afford (4R)-4-(1-hydroxypropyl)-1-[(1R)-1-(4-methoxyphenyl)ethyl]pyrrolidin-2-one as a mixture of diastereomers. The diastereomers were separated by chiral HPLC (CHIRALPAK AD), and the earlier eluting diastereomer was collected to afford (R)-4-((R)-1-hydroxypropyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.23. This compound is the later eluting diastereomer under RP-HPLC conditions (Gemini column, water/acetonitrile/TFA).

Provenance & Evidence