Benzaldehyde → Isoquinoline

HRID 333988Notes

Reaction equation

HRID 333988 reaction equation
[CH:1](=O)[C:2]1C=CC=CC=1.CO[C:11]1[CH:18]=[CH:17][C:14]([CH2:15][NH2:16])=[CH:13][CH:12]=1.FC(F)(F)C(O)=O>CCO>[CH:15]1[C:14]2[C:13](=[CH:12][CH:11]=[CH:18][CH:17]=2)[CH:2]=[CH:1][N:16]=1

Participants

5

Reactant 3

HCID 240BenzaldehydeHCID 6422Trifluoroacetic acidHCID 754524-Methoxybenzylamine

Product 1

HCID 8405Isoquinoline

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of benzaldehyde AB (2.0 g, 11.13 mmol) in EtOH (25 mL) were added 4-methoxybenzylamine (PMBNH2; 1.91 g, 13.92 mmol) and a catalytic amount of trifluoroacetic acid (TFA; 5 mol %) at RT, and the mixture was gradually heated to reflux temperature under inert atmosphere. After completion of reaction (8 h, monitored by TLC), the reaction mixture was cooled to RT and concentrated under reduced pressure. The obtained solid residue was subjected to crystallization (50% CH2Cl2/pentane) to afford colorless crystalline isoquinoline derivative AC (2.0 g, 6.69 mmol, 60%). 1H NMR (500 MHz, CDCl3): δ 8.75 (s, 1H), 7.72 (s, 1H), 7.45 (d, J=8.5 Hz, 1H), 7.38 (d, J=8.5 Hz, 1H), 7.32 (d, J=9.0 Hz, 2H), 6.89 (d, J=9.0 Hz, 2H), 6.46 (s, 1H), 5.02 (br s, 1H), 4.43 (s, 2H), 3.80 (s, 3H). MS (ESI): m/z 299 [M+H]+.

Workup

  1. temperatureto reflux temperature under inert atmosphere
  2. customAfter completion of reaction (8 h, monitored by TLC)
  3. concentrationconcentrated under reduced pressure
  4. customThe obtained solid residue was subjected to crystallization (50% CH2Cl2/pentane)

Sources & evidence

ORD record
ord-7126ff9360034ec3a394c27a92361bc5
Source dataset
uspto-grants-2014_11
Patent number
US08883797B2

Reaction notes

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