Sodium hydride → 1-(3-Methoxy-propyl)-3-methyl-1H-indole-6-carboxylic acid methyl ester

HRID 1158386Notes

Reaction equation

HRID 1158386 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([C:9]([CH3:14])=[CH:10][NH:11]2)=[CH:7][CH:6]=1)=[O:4].[H-].[Na+].Br[CH2:18][CH2:19][CH2:20][O:21][CH3:22]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([C:9]([CH3:14])=[CH:10][N:11]2[CH2:18][CH2:19][CH2:20][O:21][CH3:22])=[CH:7][CH:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 5245511-Bromo-3-methoxypropane2×HCID 21938240Methyl 3-methyl-1H-indole-6-carboxylate

Product 1

HCID 675419721-(3-Methoxy-propyl)-3-methyl-1H-indole-6-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of 3-methyl-1H-indole-6-carboxylic acid methyl ester (2.5 g, 13.2 mmol) in DMF (25 mL), a solution of NaH (580 mg, 14.5 mmol, 60% dispension in grease) in DMF (25 mL) is slowly added under a N2 atmosphere. The mixture is stirred at 80° C. for 20 min, and cooled to RT before the addition of 1-bromo-3-methoxypropane (4.04 g, 26.4 mmol). The resulting mixture is stirred for 24 h. 1-Bromo-3-methoxypropane (2.02 g, 13.2 mmol) and NaH (580 mg, 14.5 mmol) are added and the mixture further stirred for 24 h to complete the reaction. The solvent is concentrated under reduced pressure and the mixture diluted with AcOEt. An aqueous saturated solution of NaHCO3 is added, the layers are separated, and the aqueous one is back-extracted with AcOEt. The combined organic extracts are dried over Na2SO4, filtered and concentrated. The crude residue is purified by flash chromatography on silica gel (eluent: c-hexane/AcOEt 80:20) to give the title compound. MS (LC-MS): 262.0 [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 mumin): 5.80 min.

Workup

  1. stirringThe resulting mixture is stirred for 24 h
  2. stirringthe mixture further stirred for 24 h
  3. customthe reaction
  4. concentrationThe solvent is concentrated under reduced pressure
  5. additionthe mixture diluted with AcOEt
  6. additionAn aqueous saturated solution of NaHCO3 is added
  7. customthe layers are separated
  8. extractionthe aqueous one is back-extracted with AcOEt
  9. dry with materialThe combined organic extracts are dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude residue is purified by flash chromatography on silica gel (eluent: c-hexane/AcOEt 80:20)

Sources & evidence

ORD record
ord-2982a258a43f42d880404a202dc9a115
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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