Proton sponge → 6,7-dimethoxy-4-phenyl-2,3,4,5-tetrahydro 1H-benz[e]isoindole hydrochloride

HRID 1089032

Reaction equation

HRID 1089032 reaction equation
C([N:8]1[CH2:16][C:15]2[C:14]3[CH:17]=[CH:18][C:19]([O:23][CH3:24])=[C:20]([O:21][CH3:22])[C:13]=3[CH2:12][CH:11]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:10]=2[CH2:9]1)C1C=CC=CC=1.CN(C)C1C2C(=CC=CC=2N(C)C)C=CC=1.[Cl:47]C(OC(Cl)C)=O>ClCCCl>[ClH:47].[CH3:22][O:21][C:20]1[C:13]2[CH2:12][CH:11]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:10]3[CH2:9][NH:8][CH2:16][C:15]=3[C:14]=2[CH:17]=[CH:18][C:19]=1[O:23][CH3:24]

Participants

5

Reactant 3

HCID 88675Proton spongeHCID 5213051-Chloroethyl chloroformateHCID 199611422-benzyl-6,7-dimethoxy-4-phenyl-2,3,4,5-tetrahydro-1H-benz[e]isoindole

Product 1

HCID 199610916,7-dimethoxy-4-phenyl-2,3,4,5-tetrahydro 1H-benz[e]isoindole hydrochlorideYield 75%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 1.0 g (2.52 mmol) of 2-benzyl-6,7-dimethoxy-4-phenyl-2,3,4,5-tetrahydro-1H-benz[e]isoindole, from Step 5, in 22 mL of 1,2-dichloroethane was added 0.11 g (0.05 mmol) of 1,8-bis(dimethylamino)naphthalene and 0 33 mL (3.15 mmol) of 1-chloroethyl chloroformate at 0° C. The solution was heated to reflux for 2 h and the solvent removed in vacuo. The residue was filtered through silica gel, eluting with 25% ethyl acetate in hexanes. After concentration under reduced pressure, methanol (20 mL) was added and the solution was heated to reflux for 30 minutes before the solvent was removed in vacuo. The product was crystallized from ethanol/diethyl ether to give 0.46 g (75% yield) of 6,7-dimethoxy-4-phenyl-2,3,4,5-tetrahydro 1H-benz[e]isoindole hydrochloride as a white solid. MS DCI: (M+H)+ 308. 1H NMR (d6DMSO) delta 3.05-3.25 (m, 2H), 3.55 (s, 3H), 3.80 (s, 3H), 3.88 (m, 1H), 4.0-4.15 (m, 2H), 4.25-4.45 (m, 2H), 6.91 (m, 1H), 7.15-7.3 (m, 3H), 7.4-7.6 (m, 3H).

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux for 2 h
  3. customthe solvent removed in vacuo
  4. filtrationThe residue was filtered through silica gel
  5. washeluting with 25% ethyl acetate in hexanes
  6. concentrationAfter concentration under reduced pressure, methanol (20 mL)
  7. additionwas added
  8. temperaturethe solution was heated
  9. temperatureto reflux for 30 minutes before the solvent
  10. customwas removed in vacuo
  11. customThe product was crystallized from ethanol/diethyl ether

Sources & evidence

ORD record
ord-547b5bb57b774bd0aabe76f0c4427d56
Source dataset
uspto-grants-1990_10
Patent number
US04963568

Linked notes

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