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

HRID 1170361Notes

Reaction equation

HRID 1170361 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-a55ac47567004121880ece9884083903
Source dataset
uspto-grants-2010_11
Patent number
US07825254B2

Reaction notes

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