Piperidine → 4-(4-((Quinolin-2-yl)methoxy)phenyl)-3-(pyridin-4-yl)but-3-en-2-one

HRID 33922

Reaction equation

HRID 33922 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:20]=[CH:19][C:16]([CH:17]=O)=[CH:15][CH:14]=1.[N:21]1[CH:26]=[CH:25][C:24]([CH2:27][C:28](=[O:30])[CH3:29])=[CH:23][CH:22]=1.N1CCCCC1>C1(C)C=CC=CC=1>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:20]=[CH:19][C:16]([CH:17]=[C:27]([C:24]2[CH:25]=[CH:26][N:21]=[CH:22][CH:23]=2)[C:28](=[O:30])[CH3:29])=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 8082PiperidineHCID 805524-PyridinylacetoneHCID 145789604-(2-quinolinylmethoxy)Benzaldehyde

Product 1

HCID 685784954-(4-((Quinolin-2-yl)methoxy)phenyl)-3-(pyridin-4-yl)but-3-en-2-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 4-((quinolin-2-yl)methoxy)benzaldehyde (2.5 g, 9.5 mmol), 1-(pyridin-4-yl)propan-2-one (1.3 g, 9.5 mmol) and piperidine (162 mg, 1.9 mmol) in toluene (50 mL) was heated at reflux for 18 h, concentrated, and the residue chromatographed on silica eluting with a gradient of ethyl acetate in hexanes giving impure title substance (2.4 g) as a yellow solid which was chromatographed again on silica eluted with 1% and 2% methanol in dichloromethane containing 0.5% concentrated ammonium hydroxide giving a 3:1 mixture of the title substance contaminated with the pyridyl starting material. Yield 2.0 g, 55%. The title substance appeared to be a 10:1 mixture of two isomers by NMR. 1H NMR (CDCl3, 400 mHz, partial) δ 2.35 (s, 3H, major isomer), 2.23 (s, 3H, minor isomer). HPLC-MS 6.09 min, m/e 381 (MH+).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 18 h
  3. concentrationconcentrated
  4. customthe residue chromatographed on silica eluting with a gradient of ethyl acetate in hexanes giving impure title substance (2.4 g) as a yellow solid which
  5. customwas chromatographed again on silica
  6. washeluted with 1% and 2% methanol in dichloromethane containing 0.5% concentrated ammonium hydroxide giving
  7. additiona 3:1 mixture of the title substance
  8. additiona 10:1 mixture of two isomers by NMR
  9. customHPLC-MS 6.09 min, m/e 381 (MH+)

Sources & evidence

ORD record
ord-cdc2826d4e884d9da32a0d7456f0a126
Source dataset
uspto-grants-2008_09
Patent number
US07429665B2

Linked notes

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