(R)-N-methoxy-1-((R)-1-(4-methoxyphenyl)ethyl)-N-methyl-5-oxopyrrolidine-3-carboxamide → (4R)-1-[(1R)-1-(4-methoxyphenyl)ethyl]-4-(prop-2-enoyl)pyrrolidin-2-one

HRID 2208981Notes

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][CH:25]=[CH2:26]>O1CCCC1.C(OCC)(=O)C>[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])[CH:25]=[CH2:26])[CH2:10][C:9]2=[O:11])[CH3:13])=[CH:19][CH:18]=1

Participants

Conditions

Temperature: -66 °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 (3R)-N-methoxy-1-[(1R)-1-(4-methoxyphenyl)ethyl]-N-methyl-5-oxopyrrolidine-3-carboxamide 1.02 (15 g, 48.96 mmol, 1.00 equiv) in tetrahydrofuran (150 mL), followed by the addition of bromo(ethenyl)magnesium in THF (1 M) (147 mL, 3.00 equiv) dropwise with stirring at −66° C. The resulting solution was stirred at −66° C. for 3 h, poured into 250 mL of water/ice and diluted with 250 mL of ethyl acetate. The resulting solution was extracted with 3×300 mL of ethyl acetate. The organic layers were combined, washed with 3×300 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum to afford (4R)-1-[(1R)-1-(4-methoxyphenyl)ethyl]-4-(prop-2-enoyl)pyrrolidin-2-one 1.19.

Workup

customInto a 500-mL 3-necked round-bottom flask purged
temperaturemaintained with an inert atmosphere of nitrogen
stirringThe resulting solution was stirred at −66° C. for 3 h
extractionThe resulting solution was extracted with 3×300 mL of ethyl acetate
washwashed with 3×300 mL of brine
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-b158bedc941a47519fe3f40c463afc0d
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09376441B2

Reaction notes

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