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(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

HRID 2208969
Notes
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Reaction equation

HRID 2208969 reaction equation
CON(C)[C:4]([C@@H:6]1[CH2:10][C:9](=[O:11])[N:8]([C@@H:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[CH3:13])[CH2:7]1)=[O:5].[CH3:23][Mg]Br>C1COCC1>[C:4]([C@H:6]1[CH2:7][N:8]([C@@H:12]([C:14]2[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=2)[CH3:13])[C:9](=[O:11])[CH2:10]1)(=[O:5])[CH3:23]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 117843172(R)-N-methoxy-1-((R)-1-(4-methoxyphenyl)ethyl)-N-methyl-5-oxopyrrolidine-3-carboxamideHCID 178418573HCID 178418573, compound

Product 1

HCID 117843425(R)-4-acetyl-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-6be3887095774313a491ba0daaba84d1
Source dataset
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09376441B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes