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

HRID 2208984Notes

Reaction equation

HRID 2208984 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].Br[Mg][CH2:25][CH3:26]>O1CCCC1>[CH3:21][O:20][C:17]1[CH:16]=[CH:15][C:14]([C@H:12]([N:8]2[CH2:7][C@H:6]([C:4](=[O:5])[CH2:25][CH3:26])[CH2:10][C:9]2=[O:11])[CH3:13])=[CH:19][CH:18]=1

Participants

4

Reactant 2

HCID 117843172(R)-N-methoxy-1-((R)-1-(4-methoxyphenyl)ethyl)-N-methyl-5-oxopyrrolidine-3-carboxamideHCID 178418443HCID 178418443, compound

Product 1

HCID 117843004(R)-1-((R)-1-(4-Methoxyphenyl)ethyl)-4-propionylpyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

Into a 500-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of N-methoxy-1-[(1R)-1-(4-methoxyphenyl)ethyl]-N-methyl-5-oxopyrrolidine-3-carboxamide 1.02 (20 g, 65.28 mmol, 1.00 equiv) in tetrahydrofuran (200 mL), followed by the addition of bromo(ethyl)magnesium in THF (1 M) (44 mL) dropwise with stirring at −10° C. The resulting solution was stirred at −10° C. for 2 h, quenched by the addition of 200 mL of water/ice and extracted with 3×500 mL of ethyl acetate. The organic layers were combined, washed with 2×500 mL of hydrogen chloride (1 M) and 3×500 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column eluting with ethyl acetate: petroleum ether (1:5-1:1) to afford (R)-1-((R)-1-(4-methoxyphenyl)ethyl)-4-propionylpyrrolidin-2-one 1.22.

Workup

  1. customInto a 500-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringThe resulting solution was stirred at −10° C. for 2 h
  4. customquenched by the addition of 200 mL of water/ice
  5. extractionextracted with 3×500 mL of ethyl acetate
  6. washwashed with 2×500 mL of hydrogen chloride (1 M) and 3×500 mL of brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under vacuum
  9. washeluting with ethyl acetate: petroleum ether (1:5-1:1)

Sources & evidence

ORD record
ord-2dae9507f37144608c25186f10ab4b54
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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