Acetyl chloride → (S)-1-Acetyl-5-biphenyl-4-ylmethyl-pyrrolidin-2-one

HRID 1021047Notes

Reaction equation

HRID 1021047 reaction equation
[C:1]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]2[NH:12][C:11](=[O:13])[CH2:10][CH2:9]2)=[CH:3][CH:2]=1.C([Li])CCC.[C:25](Cl)(=[O:27])[CH3:26]>C1COCC1>[C:25]([N:12]1[C@H:8]([CH2:7][C:4]2[CH:3]=[CH:2][C:1]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)=[CH:6][CH:5]=2)[CH2:9][CH2:10][C:11]1=[O:13])(=[O:27])[CH3:26]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 58160438(S)-5-[(Biphenyl-4-yl)methyl]pyrrolidin-2-oneHCID 178418339Butyllithium

Product 1

HCID 59318478(S)-1-Acetyl-5-biphenyl-4-ylmethyl-pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

(S)-5-biphenyl-4-ylmethylpyrrolidin-2-one (1-a, R1=H) (5 g, 19.9 mmol) is dissolved in THF (50 ml). The mixture is cooled to −78° C. and n-butyllithium (14 ml, 1.6 M) added. After 0.5 h, acetyl chloride (1.7 ml, 24 mmol) is added and the mixture is allowed to warm to room temperature. After 1 h, the mixture is quenched with saturated ammonium chloride (40 ml) and water (10 ml) and ethyl acetate (20 ml) are added. The organic phase is washed with brine, dried (MgSO4) and concentrated in vacuo to give (S)-1-Acetyl-5-biphenyl-4-ylmethyl-pyrrolidin-2-one (1-a, R1=Ac). 1H NMR (CDCl3): 1.84 (1H), 1.93 (1H), 2.30 (1H), 2.32 (1H), 2.50 (3H), 2.72 (1H), 3.09 (1H), 4.56 (1H), 7.20 (2H), 7.28 (1H), 7.37 (2H), 7.49 (4H).

Workup

  1. temperatureto warm to room temperature
  2. waitAfter 1 h
  3. customthe mixture is quenched with saturated ammonium chloride (40 ml) and water (10 ml) and ethyl acetate (20 ml)
  4. additionare added
  5. washThe organic phase is washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-90681ecb4c1e4512be8949180566da48
Source dataset
uspto-grants-2014_05
Patent number
US08716495B2

Reaction notes

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