Sodium Iodide → HCID 66884972, compound

HRID 2353018Notes

Reaction equation

HRID 2353018 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:17]=1[NH:16][CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:20][O:21][CH:22]([O:39][CH3:40])[CH2:23][CH2:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][CH2:33]OS(C)(=O)=O)=[CH:28][CH:27]=1.[I-].[Na+]>CN(C)C=O.O>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:17]=1[N:16]([CH2:33][CH2:32][C:29]1[CH:28]=[CH:27][C:26]([O:25][CH2:24][CH2:23][CH:22]([O:39][CH3:40])[O:21][CH3:20])=[CH:31][CH:30]=1)[CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 2607987-(Benzyloxy)-1H-indoleHCID 86627980HCID 86627980, compound

Product 1

HCID 66884972HCID 66884972, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-(2-hydroxyethyl)phenol (1 g), 3-bromopropionaldehyde dimethyl acetal (1.02 mL), cesium carbonate (2.83 g) and a catalytic amount of sodium iodide in acetone (15 mL) was stirred at room temperature overnight. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on aminopropylated silica gel (eluent: n-hexane/ethyl acetate=1/1) to give 3-[4-(2-hydroxy-ethyl)phenyloxy]propionaldehyde dimethyl acetal (1.22 g). This material was dissolved in methylene chloride (15 mL). To the solution were added triethylamine (0.85 mL) and methanesulfonyl chloride (0.43 mL) under ice-cooling, and the mixture was stirred for 1 hour. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The ethyl acetate solution was washed with 0.5 mol/L hydrochloric acid, water and brine successively, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give 3-[4-(2-methanesulfonyloxyethyl)-phenyloxy]propionaldehyde dimethyl acetal (1.49 g). To a solution of 7-benzyloxy-1H-indole (1.04 g) in N,N-dimethyl-formamide (10 mL) was added sodium hydride (55% 0.25 g) under ice-cooling, and the mixture was stirred for 10 minutes. To the reaction mixture were added the above 3-[4-(2-methane-sulfonyloxyethyl)phenyloxy]propionaldehyde dimethyl acetal (1.49 g) and a catalytic amount of sodium iodide, and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with diethyl ether. The extract was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=6/1-5/1) to give 7-benzyloxy-1-{2-[4-(3,3-dimethoxypropoxy)phenyl]ethyl}-1H-indole. This material was dissolved in tetrahydrofuran (10 mL). To the solution was added 10% palladium-carbon powder (0.5 g), and the mixture was stirred at room temperature under a hydrogen atmosphere for 5 hours. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure to give the title compound (1.57 g).

Workup

  1. temperaturecooling
  2. extractionthe resulting mixture was extracted with diethyl ether
  3. washThe extract was washed with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=6/1-5/1)

Sources & evidence

ORD record
ord-c187cb67d88a4a7c8eabb618381375b2
Source dataset
uspto-grants-2010_07
Patent number
US07749972B2

Reaction notes

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