Sodium Iodide → [5-fluoro-(4-methanesulfonyl-2-trifluoromethyl-benzyl)-2-methyl-1H-indol-3-yl]-acetic acid ethyl ester

HRID 1364583Notes

Reaction equation

HRID 1364583 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([F:15])[CH:13]=2)[NH:8][C:7]=1[CH3:16])[CH3:2].[H-].[Na+].Br[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][C:23]=1[C:32]([F:35])([F:34])[F:33].[I-].[Na+]>CS(C)=O.O>[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([F:15])[CH:13]=2)[N:8]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][C:23]=2[C:32]([F:34])([F:33])[F:35])[C:7]=1[CH3:16])[CH3:2]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 11665843Ethyl (5-fluoro-2-methyl-1H-indol-3-yl)acetateHCID 513420492-(Bromomethyl)-5-(methylsulphonyl)benzotrifluoride2×

Product 1

HCID 66936503[5-fluoro-(4-methanesulfonyl-2-trifluoromethyl-benzyl)-2-methyl-1H-indol-3-yl]-acetic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a stirring solution of (5-fluoro-2-methyl-1H-indol-3-yl)-acetic acid ethyl ester (100 mg, 0.43 mmol) in dry DMSO (2 ml) at room temperature, is added sodium hydride (26 mg, 0.65 mmol) as a 60% dispersion in mineral oil. After stirring at room temperature for 30 mins, 1-bromomethyl-4-methanesulfonyl-2-trifluoromethyl-benzene (216 mg, 0.68 mmol) (intermediate 1c) and sodium iodide (102 mg, 0.68 mmol) are added. The reaction mixture is stirred at room temperature for 60 h. The reaction mixture is poured into water (20 ml) and extracted with EtOAc (20 ml). The organic phase is dried (MgSO4) and evaporated to dryness in vacuo. The crude product is purified by reverse phase chromatography on a C18 Isolute™ cartridge, eluting in 0-100% MeCN in water, using a FlashMaster Personal™ and GradMaster™; [M+H]+ 472.

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 60 h
  2. extractionextracted with EtOAc (20 ml)
  3. dry with materialThe organic phase is dried (MgSO4)
  4. customevaporated to dryness in vacuo
  5. customThe crude product is purified by reverse phase chromatography on a C18 Isolute™ cartridge
  6. washeluting in 0-100% MeCN in water

Sources & evidence

ORD record
ord-c691e0def566484d875cf2530e62a006
Source dataset
uspto-grants-2011_02
Patent number
US07888383B2

Reaction notes

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