Sodium hydride → methyl 2-(2,4-bismethoxymethoxyphenyl)-3-cyclohexyl-1-[2-(tetrahydropyran-2-yloxy)ethyl]-1H-indole-6-carboxylate

HRID 1012247Notes

Reaction equation

HRID 1012247 reaction equation
[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH2:12][O:13][CH3:14])[CH:8]=[CH:7][C:6]=1[C:15]1[NH:16][C:17]2[C:22]([C:23]=1[CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)=[CH:21][CH:20]=[C:19]([C:30]([O:32][CH3:33])=[O:31])[CH:18]=2.[H-].[Na+].Br[CH2:37][CH2:38][O:39][CH:40]1[CH2:45][CH2:44][CH2:43][CH2:42][O:41]1.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH2:12][O:13][CH3:14])[CH:8]=[CH:7][C:6]=1[C:15]1[N:16]([CH2:37][CH2:38][O:39][CH:40]2[CH2:45][CH2:44][CH2:43][CH2:42][O:41]2)[C:17]2[C:22]([C:23]=1[CH:24]1[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]1)=[CH:21][CH:20]=[C:19]([C:30]([O:32][CH3:33])=[O:31])[CH:18]=2

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyranHCID 516892Sodium BicarbonateHCID 11995225methyl 2-(2,4-bismethoxymethoxyphenyl)-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 58826635methyl 2-(2,4-bismethoxymethoxyphenyl)-3-cyclohexyl-1-[2-(tetrahydropyran-2-yloxy)ethyl]-1H-indole-6-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 2-(2,4-bismethoxymethoxyphenyl)-3-cyclohexyl-1H-indole-6-carboxylate (16.9 g, 37.3 mmol) in N,N-dimethylformamide (120 ml) was added sodium hydride (2.1 g, 52.2 mmol) under ice-cooling, and the mixture was stirred for 20 min. To the reaction mixture was added 2-(2-bromoethoxy)tetrahydro-2H-pyran (8.5 ml, 55.9 mmol), and the mixture was stirred at room temperature for 4 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure to give methyl 2-(2,4-bismethoxymethoxyphenyl)-3-cyclohexyl-1-[2-(tetrahydropyran-2-yloxy)ethyl]-1H-indole-6-carboxylate as a crude product. The obtained compound was used in Step 5 without further purification.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at room temperature for 4 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationAfter filtration
  7. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-2daa9d607cee46df832cc8e2bdd2fe56
Source dataset
uspto-grants-2011_07
Patent number
US07977331B1

Reaction notes

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