Ammonia → methyl 1-methyl-1H-indole-2-carboxylate

HRID 1770123Notes

Reaction equation

HRID 1770123 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([O:12][CH3:13])=[O:11].S(OC)(O[CH3:18])(=O)=O.C(=O)([O-])[O-].[K+].[K+].N>CC(C)=O>[CH3:18][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([O:12][CH3:13])=[O:11]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 6497Dimethyl SulfateHCID 11430Potassium CarbonateHCID 70992Methyl 1H-indole-2-carboxylate

Product 1

HCID 258548methyl 1-methyl-1H-indole-2-carboxylate

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A stirred suspension of methyl 1H-indole-2-carboxylate (5.0 g), dimethyl sulphate (9 ml) and potassium carbonate (10.4 g) in dry acetone (200 ml) was heated under reflux for 24 h. After cooling to room temperature 5% ammonia solution (50 ml) was added and the mixture stirred for 2 hours. The solvent was removed in vacuo and the residue partitioned between dichloromethane and water. The organic layer was dried and the solvent evaporated to give methyl 1-methyl-1H-indole-2-carboxylate (5.4 g) as a white solid; IR (CHBr3) max 1695 cm-1. The ester was treated with ethylenediamine and trimethylaluminium as described in Example 1(a). Purification via column chromatography on silica eluting with 5% v/v methanolic ammonia in dichloromethane gave 2-(2-imidazolin-2-yl)-1-methyl-1H-indole as a white solid. The hydrochloride salt was prepared as in Example 3 and that recrystallised from ethanol/diethyl ether; mp 290°-295° C. (decomp) (Literature mp 260°-280° C. (decomp) D. J. Hlasta, D. Luttinger, M. H. Perrone, M. J. Silbernagel, S. J. Ward and D. R. Haubrich, J. Med. Chem. 1967, 30, 1555).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 24 h
  3. additionwas added
  4. customThe solvent was removed in vacuo
  5. customthe residue partitioned between dichloromethane and water
  6. customThe organic layer was dried
  7. customthe solvent evaporated

Sources & evidence

ORD record
ord-15b9d966c7e543cb820b379a86409b90
Source dataset
uspto-grants-1995_01
Patent number
US05385919

Reaction notes

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