Trifluoroacetic acid → [3-(4-Benzenesulfonylthiazol-5-ylmethyl)-5-fluoro-2-methylindol-1-yl]acetic acid methyl ester

HRID 1944482Notes

Reaction equation

HRID 1944482 reaction equation
[CH3:1][O:2][C:3](=[O:16])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([F:14])=[CH:11][CH:12]=2)[CH:7]=[C:6]1[CH3:15].[C:17]1([S:23]([C:26]2[N:27]=[CH:28][S:29][C:30]=2[CH:31]=O)(=[O:25])=[O:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(=O)([O-])O.[Na+].ClCCCl>[CH3:1][O:2][C:3](=[O:16])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([F:14])=[CH:11][CH:12]=2)[C:7]([CH2:31][C:30]2[S:29][CH:28]=[N:27][C:26]=2[S:23]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)(=[O:24])=[O:25])=[C:6]1[CH3:15]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 58247161Methyl 2-(5-fluoro-2-methyl-1H-indol-1-yl)acetateHCID 866522084-Benzenesulfonylthiazole-5-carbaldehyde

Product 1

HCID 67044096[3-(4-Benzenesulfonylthiazol-5-ylmethyl)-5-fluoro-2-methylindol-1-yl]acetic acid methyl esterYield 48.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of (5-fluoro-2-methylindol-1-yl)acetic acid methyl ester (0.2 g), 4-benzenesulfonylthiazole-5-carbaldehyde (0.23 g) and 1,2-dichloroethane (7.0 mL) at 0° C. was treated dropwise with a mixture of triethylsilane (2.2 mL), trifluoroacetic acid (0.6 mL) and 1,2-dichloroethane (2.0 mL), and the resulting mixture was stirred at room temperature overnight. The mixture was cooled to 0° C. and diluted with saturated aqueous sodium hydrogen carbonate solution. The phases were separated and the organic phase was dried over magnesium sulfate and concentrated under reduced pressure. The residue purified by column chromatography on silica gel, eluting with a mixture of ethyl acetate and dichloromethane (0:1 to 1:4 by volume) to afford the title compound as a white foam (0.20 g).

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. customThe phases were separated
  3. dry with materialthe organic phase was dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue purified by column chromatography on silica gel
  6. washeluting with a mixture of ethyl acetate and dichloromethane (0:1 to 1:4 by volume)

Sources & evidence

ORD record
ord-8c97b2c6e28c4cf296e6d38813abe197
Source dataset
uspto-grants-2013_03
Patent number
US08394836B2

Reaction notes

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