Sodium hydride → HCID 68504024, compound

HRID 1713996Notes

Reaction equation

HRID 1713996 reaction equation
[H-].[Na+].[Br:3][C:4]1[NH:5][C:6]2[C:11]([C:12]=1[CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)=[CH:10][CH:9]=[C:8]([C:19]([O:21][CH3:22])=[O:20])[CH:7]=2.N1C2C(=CC=C(C(OC)=O)C=2)C=C1.Br[CH2:37][CH:38]1[O:42][CH2:41][CH2:40][O:39]1>CN(C=O)C>[Br:3][C:4]1[N:5]([CH2:37][CH:38]2[O:42][CH2:41][CH2:40][O:39]2)[C:6]2[C:11]([C:12]=1[CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)=[CH:10][CH:9]=[C:8]([C:19]([O:21][CH3:22])=[O:20])[CH:7]=2

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 780681,3-Dioxolane, 2-(bromomethyl)-HCID 639844Methyl indole-6-carboxylateHCID 11175076Methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 68504024HCID 68504024, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NaH (1.5 eq, 60% dispersion in mineral oil) was added to a solution of methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (prepared as described in published International Patent application WO 2004/065367, from commercially available methyl indole-6-carboxylate) in DMF (0.1 M) and once effervescence had subsided the solution was stirred at RT for a further 30 min. 2-bromomethyl-1,3-dioxolane (4 eq) and catalytic (0.025 eq) KI were then added and the mixture heated at 50° C. for 36 h. The reaction mixture was then allowed to cool to RT, quenched with aqueous HCl (1 N) and extracted with EtOAc. The organics were washed with aqueous HCl (1 N) (3×), water and brine before being dried over Na2SO4, filtered and the solvent evaporated in vacuo. Purification was by flash chromatography (10% EtOAc/PE) to give a pale yellow solid that was triturated with Et2O/PE) to afford the title compound as a white solid (69%); MS (ES+) m/z 422 (M+H)+, m/z 424 (M+H)+.

Workup

  1. customprepared
  2. temperaturethe mixture heated at 50° C. for 36 h
  3. temperatureto cool to RT
  4. customquenched with aqueous HCl (1 N)
  5. extractionextracted with EtOAc
  6. washThe organics were washed with aqueous HCl (1 N) (3×), water and brine
  7. dry with materialbefore being dried over Na2SO4
  8. filtrationfiltered
  9. customthe solvent evaporated in vacuo
  10. customPurification
  11. customto give a pale yellow solid
  12. customthat was triturated with Et2O/PE)

Sources & evidence

ORD record
ord-7d85f69b9097465c9b6d3ab7f704b020
Source dataset
uspto-grants-2010_09
Patent number
US07795247B2

Reaction notes

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