Piperidine → trans-3-(5-phenylmethoxy-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one

HRID 570623Notes

Reaction equation

HRID 570623 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[CH:18]=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:20]([C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1)(=[O:22])[CH3:21].N1CCCCC1.C(OCC)(=O)C>CO>[C:2]1([CH2:1][O:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[NH:14][CH:13]=[C:12]3/[CH:18]=[CH:21]/[C:20]([C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)=[O:22])[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8082PiperidineHCID 8857Ethyl AcetateHCID 142824-AcetylpyridineHCID 813985-(phenylmethoxy)-1H-indole-3-carbaldehyde

Product 1

HCID 70685937trans-3-(5-phenylmethoxy-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In a dried, 25 mL round bottom flask under argon, 5-benzyloxyindole-3-carboxaldehyde (100 mg, 0.40 mmol) was dissolved in anhydrous methanol (3 mL). 4-Acetyl-pyridine (75 μL, 0.68 mmol) and piperidine (20 μL, 0.2 mmol) were added. The reaction was stirred under reflux, during which a crude yellow solid precipitated. The solid was filtered, rinsed with cold methanol and dried under vacuum. This crude product (107 mg) was purified from residual aldehyde by column chromatography in ethyl acetate:hexanes (1:1-3:1 gradient), yielding pure, yellow solid (70 mg, 49%). 1H NMR (600 MHz, d6-DMSO): δ 8.837-8.827 (dd, J1=4.5, J2=1.5, 2H, pyr-2,6H), 8.148-8.143 (d, J=3.0, 1H, indole-2H), 8.095-8.069 (d, J=15.6, 1H, C═CH), 7.932-7.922 (dd, J1=4.5, J2=1.5, 2H, pyr-3,5H), 7.556-7.553 (d, J=1.8, 1H, indole-4H), 7.523-7.511 (d, J=7.2, 2H, phenyl-2,6H), 7.460-7.434 (d, J=15.6, 1H, C═CH), 7.411-7.370 (m, 3H, phenyl-3,5H, indole-7H), 7.330-7.306 (t, J=7.2, 1H, phenyl-4H), 6.979-6.961 (dd, J1=8.4, J2=2.4, 1H, indole-6H), 5.252 (s, 2H, methylene). 13C NMR (150 MHz, d6-DMSO): 188.4, 154.1, 150.7, 144.9, 140.9, 137.7, 134.6, 132.5, 128.4, 127.7, 127.6, 125.8, 121.5, 114.2, 113.3, 113.1, 112.7, 104.1, 69.8. Melting point: 218-221° C. TLC (in 4:1 ethyl acetate:hexanes) Rf=0.26. Elemental analysis calculated (for C23H19N2O2.0.2C6H14.0.05H2O): C, 78.02; H, 5.93; N, 7.52. found: C, 77.69; H, 5.62; N, 7.24.

Workup

  1. temperatureunder reflux, during which a crude yellow solid
  2. customprecipitated
  3. filtrationThe solid was filtered
  4. washrinsed with cold methanol
  5. customdried under vacuum
  6. customThis crude product (107 mg) was purified from residual aldehyde by column chromatography in ethyl acetate:hexanes (1:1-3:1 gradient)
  7. customyielding pure

Sources & evidence

ORD record
ord-c4417044b9d84bec8b2ba2ae627e1a68
Source dataset
uspto-grants-2015_05
Patent number
US09023871B2

Reaction notes

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