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

Temperature

-10 °C

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.

1. customequipped with a thermocouple
2. customreached −10° C
3. additionThe aforementioned catalyst mixture was then added in one portion
4. washwashing with additional MeCN (2×1 mL)
5. temperaturewas then warmed to 0° C
6. waitAfter an additional 4.5 h
7. customThe phases were separated
8. extractionthe aqueous phase was extracted with EtOAc (50 mL)
9. dry with materialThe combined organic phase was dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe product was purified by silica gel chromatography (35% to 50% acetone in hexanes)

ORD record

ord-44e884ba8bba495bb2d514b5b1f6d702

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09376441B2