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

Temperature

0 °C

A solution of (R)-N-methoxy-1-((R)-1-(4-methoxyphenyl)ethyl)-N-methyl-5-oxopyrrolidine-3-carboxamide 1.02 (6.87 g, 22.4 mmol) in THF (70 mL) was cooled to an internal temperature of 19° C. under Ar. Methylmagnesium bromide (3 M in Et2O, 14.9 mL, 44.7 mmol) was added in portions over ca. 10 min to keep the internal temperature below 10° C. The resulting mixture was stirred for 1 h, by which time the internal temperature had reached −12° C., and was then warmed in an ice bath to 0° C. After an additional 50 min, the reaction was quenched with saturated aqueous NH4Cl (150 mL) and was diluted with EtOAc (150 mL) and water to dissolve solids. The phases were separated, and the aqueous phase was extracted with EtOAc (100 mL). The combined organic phase was dried over Na2SO4, filtered, and concentrated onto 25 g silica gel. The product was purified by silica gel chromatography (15% to 45% acetone in hexanes) to afford (R)-4-acetyl-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.03.

1. customthe internal temperature below 10° C
2. customhad reached −12° C.
3. waitAfter an additional 50 min
4. customthe reaction was quenched with saturated aqueous NH4Cl (150 mL)
5. additionwas diluted with EtOAc (150 mL) and water
6. dissolutionto dissolve solids
7. customThe phases were separated
8. extractionthe aqueous phase was extracted with EtOAc (100 mL)
9. dry with materialThe combined organic phase was dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated onto 25 g silica gel
12. customThe product was purified by silica gel chromatography (15% to 45% acetone in hexanes)

ORD record

ord-6be3887095774313a491ba0daaba84d1

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09376441B2