Formic Acid → (R)-4-((R)-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

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Reaction Conditions

Reaction Steps

In a separate flask, a solution of (R)-4-acetyl-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.03 (1.8 g, 6.9 mmol) in MeCN (34 mL) was cooled to an internal temperature of −10° C. under Ar in a jacketed 3-neck flask equipped with a thermocouple. Triethylamine (5.1 mL, 36 mmol) was added during the cooling ramp at 0° C. Formic acid (0.525 mL, 13.9 mmol) was added once the internal temperature reached −10° C. The aforementioned catalyst mixture was then added in one portion, washing with additional MeCN (2×1 mL). The resulting orange solution was stirred for 18 h at −10° C. and was then warmed to 0° C. After an additional 4.5 h, hydrochloric acid (3 M, 13 mL, 39 mmol) was added followed by EtOAc (50 mL) and brine (30 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (50 mL). The combined organic phase was dried over Na2SO4, filtered, and concentrated. The product was purified by silica gel chromatography (35% to 50% acetone in hexanes) to afford (R)-4-((R)-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.04.

Provenance & Evidence