Sulfuric Acid → (R)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3,3-dimethyl-pyrrolidin-2-one

HRID 882514Notes

Reaction equation

HRID 882514 reaction equation
[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]2[N:12]([C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])[C:11](=[O:19])[C@H:10]([CH3:20])[CH2:9]2)=[CH:3][CH:2]=1.[CH:27]([N-]C(C)C)(C)C.[Li+].CI.NCCC(CN)O.S(=O)(=O)(O)O>C1COCC1>[C:1]1([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]2[N:12]([C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])[C:11](=[O:19])[C:10]([CH3:27])([CH3:20])[CH2:9]2)=[CH:5][CH:6]=1

Participants

7

Reactant 5

HCID 1118Sulfuric AcidHCID 6328Methyl iodideHCID 1646562-HydroxyputrescineHCID 2724682Lithium diisopropylamideHCID 66738857(3R,5S)-5-biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3-methylpyrrolidin-2-one

Product 1

HCID 59318477(R)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3,3-dimethyl-pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-30 °C

Procedure

10 g (3R,5S)-5-biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3-methylpyrrolidin-2-one (2-a, R1=Piv) is added to THF (100 ml). The mixture is cooled to −30° C. Lithium diisopropylamide (17.16 ml, 2 M) is added and the mixture is stirred for 1 h. Methyl iodide (5.4 ml) is added and the mixture is stirred for 3 h. Aminoethylethanolamine (6.1 ml) is added and the mixture is warmed to 40° C. and stirred for 15 min. Sulphuric acid (12 g) is then added. The mixture is concentrated in vacuo and the residue taken up in toluene. The phases are separated. The organic phase is concentrated in vacuo and taken up in methanol (300 ml) at reflux. On cooling, the precipitate is collected by filtration to give (R)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3,3-dimethyl-pyrrolidin-2-one. 1H NMR (DMSO): 1.04 (3H), 1.15 (3H), 1.28 (9H), 1.72 (1H), 1.38 (1H), 2.59 (1H), 3.14 (1H), 4.37 (1H), 7.31 (3H), 7.45 (2H), 7.62 (4H).

Workup

  1. stirringthe mixture is stirred for 3 h
  2. temperaturethe mixture is warmed to 40° C.
  3. stirringstirred for 15 min
  4. concentrationThe mixture is concentrated in vacuo
  5. customThe phases are separated
  6. concentrationThe organic phase is concentrated in vacuo
  7. temperatureat reflux
  8. temperatureOn cooling
  9. filtrationthe precipitate is collected by filtration

Sources & evidence

ORD record
ord-a28ad0b570f341e5825e61dcd9128d59
Source dataset
uspto-grants-2015_03
Patent number
US08993785B2

Reaction notes

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