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

HRID 1191481ノート

反応式

HRID 1191481 の反応式
[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]

参加物

8

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 6342Acetonitrile溶媒

実験手順

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 cooled 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

後処理

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

出典と根拠

ORDレコード
ord-117efd95868e490597fd617066577970
出典データセット
uspto-grants-2014_03
特許番号
US08680115B2

反応ノート

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