Water → 1-(3,4-dihydroquinolin-1(2H)-ylmethyl)-4-propylpyrrolidin-2-one

HRID 1924299Notes

Reaction equation

HRID 1924299 reaction equation
[NH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Cl[CH2:14][N:15]1[CH2:19][CH:18]([CH2:20][CH2:21][CH3:22])[CH2:17][C:16]1=[O:23].O>CN(C=O)C>[N:1]1([CH2:14][N:15]2[CH2:19][CH:18]([CH2:20][CH2:21][CH3:22])[CH2:17][C:16]2=[O:23])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 694601,2,3,4-TetrahydroquinolineHCID 536292161-(Chloromethyl)-4-propylpyrrolidin-2-one

Product 1

HCID 577430341-(3,4-dihydroquinolin-1(2H)-ylmethyl)-4-propylpyrrolidin-2-oneYield 28%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 1,2,3,4-tetrahydroquinoline x158 (400 mg, 3 mmol, 1 eq) in DMF (7 ml) maintained under argon is added NaH (60% in mineral oil; 120 mg, 3 mmol, 1 eq). The reaction mixture is stirred for three hour at room temperature, then a solution of 1-(chloromethyl)-4-propylpyrrolidin-2-one x63 in DMF (1 M, 3 ml, 3 mmol, 1 eq) is added. The reaction mixture is stirred for 20 hours at the same temperature. Water (70 ml) is added and the resulting mixture is extracted with ethyl acetate (30 ml). The organic phase is washed twice with water and dried over Na2SO4. After filtration and evaporation, the crude product is purified by two consecutive chromatographies on silicagel (CH2Cl2/MeOH gradient, then CH2Cl2). Pure 1-(3,4-dihydroquinolin-1(2H)-ylmethyl)-4-propylpyrrolidin-2-one 295 is obtained as syrup (231 mg).

Workup

  1. stirringThe reaction mixture is stirred for 20 hours at the same temperature
  2. extractionthe resulting mixture is extracted with ethyl acetate (30 ml)
  3. washThe organic phase is washed twice with water
  4. dry with materialdried over Na2SO4
  5. filtrationAfter filtration and evaporation
  6. customthe crude product is purified by two consecutive chromatographies on silicagel (CH2Cl2/MeOH gradient

Sources & evidence

ORD record
ord-ba066965ab104e25b831ecd812d69164
Source dataset
uspto-grants-2012_05
Patent number
US08178533B2

Reaction notes

Loading…