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

HRID 1364581Notes

Reaction equation

HRID 1364581 reaction equation
[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][C:6]=1[CH3:14].[H-].[Na+].[Na+].[I-].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]>CN(C=O)C.CCOC(C)=O.O>[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]([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:6]=1[CH3:14]

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 10774509Sbb044946HCID 513420492-(Bromomethyl)-5-(methylsulphonyl)benzotrifluoride

Product 1

HCID 66936534[1-(4-methanesulfonyl-2-trifluoromethyl-benzyl)-2-methyl-1H-indol-3-yl]-acetic acid methyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirring solution of (2-methyl-1H-indol-3-yl)-acetic acid methyl ester (2.0 g, 10.5 mmol) in dry DMF (25 ml) at 0° C., is added portionwise NaH (0.46 g, 11.5 mmol) as a 60% dispersion in mineral oil. The reaction mixture is stirred at 0° C. for 1.5 h then NaI (1.72 g, 11.5 mmol) and 1-bromomethyl-4-methanesulfonyl-2-trifluoromethyl-benzene (3.65 g, 11.5 mmol) are added. The reaction mixture is stirred at room temperature for 16 h. The reaction mixture is poured into water (100 ml) and EtOAc (50 ml) is added. An emulsion is formed which is filtered. Brine (20 ml) is added to the filtrate and the organic phase is separated and dried (MgSO4). Evaporation in vacuo affords a brown oil. Purification by flash chromatography on silica gel using 5:1 iso-hexane:EtOAc, increasing polarity up to 3:1 iso-hexane:EtOAc, gives the desired product; [M+H]+ 440.

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 16 h
  2. additionis added
  3. customAn emulsion is formed which
  4. filtrationis filtered
  5. additionBrine (20 ml) is added to the filtrate
  6. customthe organic phase is separated
  7. dry with materialdried (MgSO4)
  8. customEvaporation in vacuo
  9. customaffords a brown oil
  10. customPurification by flash chromatography on silica gel using 5:1 iso-hexane
  11. temperatureEtOAc, increasing polarity up to 3:1 iso-hexane

Sources & evidence

ORD record
ord-d8390c2ef32f457bb1b59e9f03c6ea18
Source dataset
uspto-grants-2011_02
Patent number
US07888383B2

Reaction notes

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