Sodium hydride → methyl 1-(3-methoxypropyl)-1H-indole-6-carboxylate

HRID 1158409Notes

Reaction equation

HRID 1158409 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].Br[CH2:17][CH2:18][CH2:19][O:20][CH3:21].[NH4+].[Cl-]>CN(C=O)C.C(Cl)Cl>[CH3:13][O:12][C:10]([C:7]1[CH:8]=[C:9]2[C:4]([CH:3]=[CH:2][N:1]2[CH2:17][CH2:18][CH2:19][O:20][CH3:21])=[CH:5][CH:6]=1)=[O:11]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 5245511-Bromo-3-methoxypropaneHCID 639844Methyl indole-6-carboxylate

Product 1

HCID 67542758methyl 1-(3-methoxypropyl)-1H-indole-6-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl indole-6-carboxylate (5.0 g, 28.5 mmol) in DMF (25 mL) is added under nitrogen, NaH-60% dispersion in oil (1.25 g, 31.3 mmol), the mixture is heated at 60° C. for 2 h, cooled to RT and 1-bromo-3-methoxypropane (8.7 g, 57.0 mmol) is added. The mixture is further stirred at 60° C. overnight. The crude mixture is poured into an aqueous solution of NH4Cl and diluted with CH2Cl2. The layers are separated and the aqueous one extracted twice with CH2Cl2. The combined organic extracts are washed with water, dried over Na2SO4, filtered and concentrated to give the title product. MS (LC-MS): 248.0 [M+H]+; tR (HPLC, Macherey-Nagel Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 ml/min): 5.69 min.

Workup

  1. customThe layers are separated
  2. extractionthe aqueous one extracted twice with CH2Cl2
  3. washThe combined organic extracts are washed with water
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-11a4d5e0096c46c08e5ebf4b50951582
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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