Trifluoroacetic acid → [5-Fluoro-2-methyl-3-(2-sulfobenzyl)indol-1-yl]acetic acid methyl ester

HRID 1944425Notes

Reaction equation

HRID 1944425 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].[Na+].[CH:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[S:26]([O-:29])(=[O:28])=[O:27])=O.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>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]([CH2:18][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[S:26]([OH:29])(=[O:28])=[O:27])=[C:6]1[CH3:15]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 3794540Sodium o-formylbenzenesulfonateHCID 58247161Methyl 2-(5-fluoro-2-methyl-1H-indol-1-yl)acetate

Product 1

HCID 86652190[5-Fluoro-2-methyl-3-(2-sulfobenzyl)indol-1-yl]acetic acid methyl esterYield 73.6%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

A mixture of (5-fluoro-2-methylindol-1-yl)acetic acid methyl ester (1.0 g), 2-formylbenzensulfonic acid sodium salt (0.94 g) and 1,2-dichloroethane (15 mL) at 0° C. was treated dropwise with a mixture of triethylsilane (4.3 mL), trifluoroacetic acid (1.0 mL) and 1,2-dichloroethane (10 mL), and the resulting mixture was stirred at room temperature for 6 hours. The mixture was extracted with ethyl acetate and the combined organic extract was dried over sodium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel, eluting with a mixture of methanol and dichloromethane (0:1 to 1:9 by volume) to afford the title compound as a purple gum (1.3 g).

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. extractionthe combined organic extract
  3. dry with materialwas dried over sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. customthe residue purified by column chromatography on silica gel
  6. washeluting with a mixture of methanol and dichloromethane (0:1 to 1:9 by volume)

Sources & evidence

ORD record
ord-e70b1af3948540bb810480d9cc1aec39
Source dataset
uspto-grants-2013_03
Patent number
US08394836B2

Reaction notes

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