Sodium Hydroxide → HCID 14625298, compound

HRID 1089309Notes

Reaction equation

HRID 1089309 reaction equation
P(Cl)(Cl)(Cl)=O.[C:6]([N:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][C:13]([O:27][CH3:28])=[C:14]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:15]=2)[CH2:10]1)(=O)[CH3:7].[C:29]([C:31]1[CH:37]=[C:36]([O:38][CH3:39])[C:35]([O:40][CH3:41])=[CH:34][C:32]=1[NH2:33])#[N:30].[OH-].[Na+]>C(Cl)Cl.O>[CH2:20]([O:19][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][C:13]=1[O:27][CH3:28])[CH2:10][N:9]([C:6](=[N:33][C:32]1[CH:34]=[C:35]([O:40][CH3:41])[C:36]([O:38][CH3:39])=[CH:37][C:31]=1[C:29]#[N:30])[CH3:7])[CH2:18][CH2:17]2)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 7359672-Amino-4,5-dimethoxybenzonitrileHCID 14625296HCID 14625296, compound

Product 1

HCID 14625298HCID 14625298, compoundYield 72.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

Phosphorus oxychloride (3.24 ml) was added over 1 minute to a stirred solution of N-acetyl-6-benzyloxy-7-methoxy-1,2,3,4-tetrahydroisoquinoline (10 g) in methylene chloride (100 ml) at 10°. After stirring for twenty minutes at room temperature, a solution of 2-cyano-4,5-dimethoxyaniline (5.72 g) in methylene chloride (80 ml) was added and the resulting suspension was heated at reflux for 16 hours. The reaction mixture was then allowed to cool, water (60 ml) was added followed by 40% sodium hydroxide to pH 8-9 with stirring for five minutes. The organic layer was then separated and the aqueous phase extracted with methylene chloride (3×50 ml). The combined organic layers were washed (H2O), dried (MgSO4) and evaporated. The residue was chromatographed on silica (Merck Art.9385) under medium pressure, eluting with methylene chloride containing gradually increasing amounts of methanol (0-10%). Some impure product-containing fractions were re-chromatographed on silica but using methylene chloride containing 2-4% methanol. The pure product-containing fractions were combined, evaporated, and the residue recrystallised from ethyl acetate to give the title compound as a colourless powder (11.02 g), m.p. 164°-5° (d).

Workup

  1. temperaturethe resulting suspension was heated
  2. temperatureat reflux for 16 hours
  3. temperatureto cool
  4. stirringwith stirring for five minutes
  5. customThe organic layer was then separated
  6. extractionthe aqueous phase extracted with methylene chloride (3×50 ml)
  7. washThe combined organic layers were washed (H2O)
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customThe residue was chromatographed on silica (Merck Art.9385) under medium pressure
  11. washeluting with methylene chloride containing gradually increasing amounts of methanol (0-10%)
  12. additionSome impure product-containing fractions
  13. customwere re-chromatographed on silica
  14. additionThe pure product-containing fractions
  15. customevaporated
  16. customthe residue recrystallised from ethyl acetate

Sources & evidence

ORD record
ord-e58adfc17bfa4ff69ac235fc0e4def94
Source dataset
uspto-grants-1990_10
Patent number
US04965360

Reaction notes

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