Benzaldehyde → Isoquinoline

HRID 1429591Notes

Reaction equation

HRID 1429591 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-7dd87fe81cfa4022bd488f5b9cd0b620
Source dataset
uspto-grants-2015_01
Patent number
US08940735B2

Reaction notes

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