N-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide → 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)aniline

HRID 45670Notes

Reaction equation

HRID 45670 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:19]=[CH:18][C:17]([NH:20]C(=O)C)=[CH:16][CH:15]=1.C[O-].[Na+]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=1

Participants

4

Reactant 2

HCID 9902940N-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamideHCID 10942334Sodium Methoxide

Product 1

HCID 99443944-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)aniline

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Into a 100-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of N-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide (2 g, 5.73 mmol, 1.00 equiv) in ethanol (20 mL). This was followed by the addition of sodium methanolate (5 g, 92.59 mmol, 16.16 equiv) in several batches, while the temperature was maintained at reflux. The resulting solution was heated to reflux overnight. The reaction was then quenched by the addition of 50 mL of water/ice. The resulting solution was extracted with 3×50 mL of ethyl acetate and the organic layers combined and concentrated under vacuum. This resulted in 1.5 g (85%) of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenamine as yellow oil. 1H-NMR (300 MHz, DMSO, ppm): δ 7.42-7.42 (1H, d, J=1.5 Hz), 6.83-6.86 (2H, d, J=8.1 Hz), 6.78-6.78 (1H, d, J=1.2 Hz), 6.48-6.51 (2H, d, J=8.4 Hz), 4.98 (2H, s), 4.02-4.06 (1H, m), 3.62-3.67 (1H, d, J=16.2 Hz), 3.43-3.48 (1H, d, J=15.9 Hz), 2.80-2.86 (1H, m), 2.37 (3H, s). MS (ES, m/z): 307 [M+H]+.

Workup

  1. customInto a 100-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. temperaturewas maintained
  4. temperatureat reflux
  5. temperatureThe resulting solution was heated
  6. temperatureto reflux overnight
  7. customThe reaction was then quenched by the addition of 50 mL of water/ice
  8. extractionThe resulting solution was extracted with 3×50 mL of ethyl acetate
  9. concentrationconcentrated under vacuum
  10. customThis resulted in 1.5 g (85%) of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenamine as yellow oil

Sources & evidence

ORD record
ord-8c8845d52bda49f7a04c7e3d9f3ef82e
Source dataset
uspto-grants-2013_09
Patent number
US08541448B2

Reaction notes

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