Methanol → 3-(2-Aminoethyl)-4-chloro-5-methoxyindole oxalate

HRID 1898995Notes

Reaction equation

HRID 1898995 reaction equation
[C:1]([CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:14][CH3:15])[C:11]=2[Cl:13])[NH:6][CH:5]=1)#[N:2].C(O)(=O)/C=C/[C:19]([OH:21])=[O:20].[CH3:24][OH:25]>CNC.[Ni]>[C:19]([OH:21])(=[O:20])[C:24]([OH:14])=[O:25].[NH2:2][CH2:1][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:14][CH3:15])[C:11]=2[Cl:13])[NH:6][CH:5]=1

Participants

6

Reactant 3

HCID 887Methanol3×HCID 444972Fumaric AcidHCID 233730472-(4-Chloro-5-methoxy-1H-indol-3-yl)acetonitrile

Product 1

HCID 233730993-(2-Aminoethyl)-4-chloro-5-methoxyindole oxalate

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 674DimethylamineSolvent

Procedure

Reductive amination of 3-cyanomethyl-4-chloro-5-methoxyindole (3.82 g, 17.3 mmol) in methanol (200 ml) and dimethylamine (40 ml) over Raney nickel for 21/2 hours at 15 p.s.i. pressure, at room temperature, followed by removal of catalyst and solvent gave a crude product containing two major components. Separation by chromatography (SiO2 ; CHCl3 /MeOH) gave two products. Part of the less polar product (650 mg of 2.13 g) was dissolved in methanol and treated with a solution of excess fumaric acid in methanol. On treatment with diethyl ether and refrigeration, the product, 3-(2-dimethylaminoethyl)-4-chloro-5-methoxyindole fumarate (494 mg) crystallised out, m.p. 223°-5° C. The whole of the more polar product was treated with a solution of oxalic acid in methanol to give 3-(2-aminoethyl)-4-chloro-5-methoxyindole oxalate. Recrystallisation from methanol gave 301 mg, dec > 230° C.

Workup

  1. custom2 hours
  2. custompressure, at room temperature, followed by removal of catalyst and solvent
  3. customgave a crude product
  4. additioncontaining two major components
  5. customSeparation by chromatography (SiO2 ; CHCl3 /MeOH)
  6. customgave two products
  7. customOn treatment with diethyl ether and refrigeration, the product, 3-(2-dimethylaminoethyl)-4-chloro-5-methoxyindole fumarate (494 mg) crystallised out
  8. additionThe whole of the more polar product was treated with a solution of oxalic acid in methanol

Sources & evidence

ORD record
ord-cc6574d1f0d04b6181cf01d6909f3bb3
Source dataset
uspto-grants-1996_11
Patent number
US05571833

Reaction notes

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