Benzaldehyde → 1,2,3,4-Tetrahydro-6-methoxy-1-phenylisoquinoline

HRID 853790Notes

Reaction equation

HRID 853790 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:9][CH2:10][NH2:11])[CH:6]=[CH:7][CH:8]=1.[CH:12](=O)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:6](=[CH:7][CH:8]=1)[CH:12]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[NH:11][CH2:10][CH2:9]2

Participants

4

Reactant 2

HCID 240BenzaldehydeHCID 748663-Methoxyphenethylamine

Product 1

HCID 117763951,2,3,4-Tetrahydro-6-methoxy-1-phenylisoquinoline

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Conditions

Temperature
60 °C

Procedure

3-Methoxyphenylethylamine (1.5 g) and benzaldehyde (1.0 mL) were reacted together in benzene (10 mL) in a modified Dean-Stark apparatus, where the side arm contained activated 3 Å molecular sieve beads. The reaction was vigorously refluxed for 1 h until a uniform solution resulted. The reaction was cooled and evaporated. The resulting residue was taken up in trifluoroacetic acid (6 mL) and heated to 60° C. for 18 h. The reaction was cooled, concentrated then partitioned between 1N sodium hydroxide (70 mL) and diethyl ether (50 mL). The organic layer was washed with 0.5 N sodium hydroxide (70 mL), dried, concentrated to 20 mL and cooled in an ice-water bath. The crystals that formed were collected and dried to give the title compound (1.90 g). MS: 240.0 (MH+); HPLC tR: 1.62 min (method D); 1H NMR (DMSO-d6+TFA-d): 7.47-7.49 (m, 3H), 7.37-7.39 (m, 2H), 6.90 (broad s, 1H), 6.79 (dd, 1H, J=2.4, 8.7 Hz), 6.66 (d, 1H, J=8.7 Hz), 5.75 (s, 1H), 3.77 (s, 3H), 3.39-3.44 (m, 2H), 3.17-3.28 (m, 1H), 3.04-3.12 (m, 1H).

Workup

  1. temperatureThe reaction was vigorously refluxed for 1 h until a uniform solution
  2. customresulted
  3. temperatureThe reaction was cooled
  4. customevaporated
  5. temperatureThe reaction was cooled
  6. concentrationconcentrated
  7. customthen partitioned between 1N sodium hydroxide (70 mL) and diethyl ether (50 mL)
  8. washThe organic layer was washed with 0.5 N sodium hydroxide (70 mL)
  9. customdried
  10. concentrationconcentrated to 20 mL
  11. temperaturecooled in an ice-water bath
  12. customThe crystals that formed
  13. customwere collected
  14. customdried

Sources & evidence

ORD record
ord-88599b8daaf2415bbd5898da16efc0ea
Source dataset
uspto-grants-2007_08
Patent number
US07256201B2

Reaction notes

Loading…