Cesium carbonate → 1-[3-(4-Butyl-piperidin-1-yl)-propyl]-6-methoxy-3,4-dihydro-1H-quinolin-2-one

HRID 969438Notes

Reaction equation

HRID 969438 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=[O:13])[CH2:7][CH2:6]2.Cl[CH2:15][CH2:16][CH2:17]I.C([O-])([O-])=O.[Cs+].[Cs+].C([O-])([O-])=O.[K+].[K+].[CH2:31]([CH:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)[CH2:32][CH2:33][CH3:34]>C(#N)C.O>[CH2:31]([CH:35]1[CH2:40][CH2:39][N:38]([CH2:15][CH2:16][CH2:17][N:9]2[C:10]3[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:12][CH:11]=3)[CH2:6][CH2:7][C:8]2=[O:13])[CH2:37][CH2:36]1)[CH2:32][CH2:33][CH3:34]

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 813631-Chloro-3-iodopropaneHCID 108884676-Methoxy-1,2,3,4-tetrahydroquinolin-2-oneHCID 132838674-Butylpiperidine

Product 1

HCID 102869221-[3-(4-Butyl-piperidin-1-yl)-propyl]-6-methoxy-3,4-dihydro-1H-quinolin-2-one

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

6-Methoxy-3,4-dihydro-1H-quinolin-2-one (108 mg, 0.61 mmol), 1-chloro-3-iodopropane (64 μl, 0.6 mmol) and Cs2CO3 (290 mg, 0.9 mmol) in acetonitrile (2 mL) were shaken at 60° C. for 14 h then the reaction was colled to room temperature. Water (5 mL) was added and the product was extracted with ethyl acetate (2×10 mL). The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The syrup was dissolved in acetonitrile (4 mL). KI (83 mg, 3.6 mmol), K2CO3 (100 mg, 0.6 mmol) and 4-butylpiperidine (83 μl, 0.5 mmol) were added and the reaction mixture was shaken at 60° C. for 16 h. Water (5 mL) was added and the product was extracted with ethyl acetate (2×10 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo. The product was purified by column chromatography (eluent: 20% methanol in ethyl acetate) to yield the title compound. Yield: 24.8 mg, 11.3%. HPLC-MS: M+1+=359.5 (UV/MS(%)=90/78). 1H NMR (400 MHz, CDCl3): δ=0.89 (3H, t), 1.12-1.34 (9H, m), 1.67 (2H, broad d), 1.85 (2H, quin.), 1.93 (2H, broad t), 2.39 (2H, t), 2.59 (2H, dd), 2.83 (2H, t), 2.90 (2H, broad d), 3.76 (3H, s), 3.94 (2H, t), 6.70 (1H, d), 6.74 (1H, dd), 7.01 (1H, d). 13C NMR (CDCl3): δ 14.3, 23.0, 25.0, 26.1, 29.2, 32.1, 32.5 (2C), 35.9, 36.4, 40.8, 54.3 (2C), 55.8, 56.3, 112.2, 114.2, 116.2 128.3, 133.4, 155.4, 169.9

Workup

  1. customwas colled to room temperature
  2. extractionthe product was extracted with ethyl acetate (2×10 mL)
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe syrup was dissolved in acetonitrile (4 mL)
  7. extractionthe product was extracted with ethyl acetate (2×10 mL)
  8. dry with materialThe organic layer was dried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customThe product was purified by column chromatography (eluent: 20% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-2ffd8b414c6b4b44b7ac315d0ef220d1
Source dataset
uspto-grants-2007_12
Patent number
US07307075B2

Reaction notes

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