Dimethylformamide → Ethyl 7-[(6-chloropyridin-2-yl)methoxy]-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxylate

HRID 1188878Notes

Reaction equation

HRID 1188878 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([O:16][C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=2)[CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:7]2.Br[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[N:30]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>CCCCCC.C(OCC)(=O)C.O>[Cl:35][C:31]1[N:30]=[C:29]([CH2:28][O:1][C:2]2[CH:3]=[C:4]([O:16][C:17]3[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=3)[CH:5]=[C:6]3[C:10]=2[NH:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:7]3)[CH:34]=[CH:33][CH:32]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 220327372-(Bromomethyl)-6-chloro-pyridineHCID 66726144Ethyl 7-hydroxy-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxylate

Product 1

HCID 86652835Ethyl 7-[(6-chloropyridin-2-yl)methoxy]-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxylateYield 54%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of ethyl 7-hydroxy-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxylate (1.39 g), 2-(bromomethyl)-6-chloropyridine (840 mg), potassium carbonate (1.02 g) and N,N-dimethylformamide (20 mL) was stirred at room temperature for 2.5 hr. Water was added to the reaction mixture, and the mixture was subjected to extraction with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained crude product was subjected to basic silica gel column chromatography (ethyl acetate:hexane=10:90-65:35, volume ratio), and the obtained solid was washed with diethyl ether to give the title compound (1.0 g, yield 54%) as white crystals. MS 501 (MH+).

Workup

  1. extractionthe mixture was subjected to extraction with ethyl acetate
  2. washThe organic layer was washed successively with water and saturated brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained crude product
  7. washthe obtained solid was washed with diethyl ether

Sources & evidence

ORD record
ord-b3f312b0d1d54e658ec4193e050ed73a
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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