Dimethylamine → 3-dimethylamino-methyl-1H-indole-6-carboxylic acid methyl ester

HRID 1272246

Reaction equation

HRID 1272246 reaction equation
[CH:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[NH:5][CH:4]=1)=[O:2].[CH3:16][NH:17][CH3:18].[BH4-].[Na+].[CH3:21]O>C(Cl)(Cl)Cl.[Cl-].[Na+].O>[NH3:5].[CH3:1][OH:2].[CH3:15][O:14][C:12]([C:8]1[CH:7]=[C:6]2[C:11]([C:3]([N:17]([CH3:18])[CH3:16])=[CH:4][N:5]2[CH3:21])=[CH:10][CH:9]=1)=[O:13]

Participants

8

Reactant 4

HCID 674DimethylamineHCID 887MethanolHCID 735867methyl 3-formyl-1H-indole-6-carboxylateHCID 4311764Sodium borohydride

Product 2

HCID 21705897Ammonia methanolYield 20%HCID 695164543-dimethylamino-methyl-1H-indole-6-carboxylic acid methyl esterYield 99%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
55 °C

Procedure

A solution of methyl 3-formylindole-6-carboxylate (8.0 g, 39.3 mmol) in 270 ml methanol is treated with dimethylamine (40% aqueous; 267 ml, 2.56 mol) at ambient temperature. After 45 minutes, NaBH4 (4.45 g, 118.1 mmol) is added, and the resulting mixture is heated at 55° C. for 3 hours. The reaction mixture is allowed to cool then is diluted with CHCl3 (200 ml) and brine (150 ml). The organic layer is washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude residue is purified by flash chromatography (SiO2; 100% ethyl acetate then 20% 2M NH3/methanol in CHCl3) to give 9.07 g of 3-dimethylamino-methyl-1H-indole-6-carboxylic acid methyl ester (99%). Amine 61 is prepared from 3-dimethylaminomethyl-1H-indole-6-carboxylic acid methyl ester by essentially following the procedures detailed in Amine 49, 1st paragraph; and Amine 51, 3rd paragraph.

Workup

  1. temperatureto cool
  2. washThe organic layer is washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude residue is purified by flash chromatography (SiO2

Sources & evidence

ORD record
ord-2595965355ff47e19b1d69e5f4a9dd03
Source dataset
uspto-grants-2007_04
Patent number
US07208505B2

Linked notes

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