4-Methylmorpholine → 1-methyl-1H-indole-2-carboxamide

HRID 1581683Notes

Reaction equation

HRID 1581683 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[C:11]([OH:13])=O.C[N:15]1CCOCC1.ClC(OCC(C)C)=O.[NH4+].[OH-]>C1COCC1>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[C:11]([NH2:15])=[O:13]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 14923Ammonium HydroxideHCID 276951H-Indole-2-carboxylic acid, 1-methyl-HCID 62365Isobutyl chloroformate

Product 1

HCID 8210631-methyl-1H-indole-2-carboxamideYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-methylindole-2-carboxylic acid (5.0 g, 28.5 mmole) in THF (100 mL) at 0° C. was added N-methylmorpholine (3.5 mL, 31.8 mmole) followed by isobutyl chloroformate (4.0 mL, 30.8 mmole) dropwise over 5 minutes. A thick slurry formed quickly. The mixture was stirred for 30 min, then conc. NH4OH (4.0 mL. 58 mmole) was added in one portion with vigorous stirring, and the cooling bath was removed. The reaction was stirred at RT for 4 hr then was concentrated to dryness. The residue was triturated with 1.0 N Na2CO3 (50 mL), filtered, washed with a small volume of cold water, and dried under vacuum to give the title compound (2.46 g, 50%) as a white solid: Silica gel TLC (5% MeOH/CHCl3) Rf0.50.

Workup

  1. customA thick slurry formed quickly
  2. customthe cooling bath was removed
  3. stirringThe reaction was stirred at RT for 4 hr
  4. concentrationthen was concentrated to dryness
  5. customThe residue was triturated with 1.0 N Na2CO3 (50 mL)
  6. filtrationfiltered
  7. washwashed with a small volume of cold water
  8. customdried under vacuum

Sources & evidence

ORD record
ord-7cceecc989e6411bae72b73b74fc5ce1
Source dataset
uspto-grants-2004_05
Patent number
US06730684B1

Reaction notes

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