Trifluoroacetic acid → {5-Fluoro-3-[3-(4-fluorobenzenesulfonyl)thiophen-2-ylmethyl]-2-methylindol-1-yl}acetic acid methyl ester

HRID 1944378Notes

Reaction equation

HRID 1944378 reaction equation
C([SiH](CC)CC)C.FC(F)(F)C(O)=O.[CH3:15][O:16][C:17](=[O:30])[CH2:18][N:19]1[C:27]2[C:22](=[CH:23][C:24]([F:28])=[CH:25][CH:26]=2)[CH:21]=[C:20]1[CH3:29].[F:31][C:32]1[CH:37]=[CH:36][C:35]([S:38]([C:41]2[CH:45]=[CH:44][S:43][C:42]=2[CH:46]=O)(=[O:40])=[O:39])=[CH:34][CH:33]=1>ClCCl.ClCCCl>[CH3:15][O:16][C:17](=[O:30])[CH2:18][N:19]1[C:27]2[C:22](=[CH:23][C:24]([F:28])=[CH:25][CH:26]=2)[C:21]([CH2:46][C:42]2[S:43][CH:44]=[CH:45][C:41]=2[S:38]([C:35]2[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=2)(=[O:39])=[O:40])=[C:20]1[CH3:29]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 58247161Methyl 2-(5-fluoro-2-methyl-1H-indol-1-yl)acetateHCID 866521803-(4-Fluorobenzenesulfonyl)thiophene-2-carbaldehyde

Product 1

HCID 67025809{5-Fluoro-3-[3-(4-fluorobenzenesulfonyl)thiophen-2-ylmethyl]-2-methylindol-1-yl}acetic acid methyl esterYield 79.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

A mixture of triethylsilane (0.79 g), trifluoroacetic acid (0.47 g) and 1,2-dichloroethane (2.0 mL) at −10° C. was treated dropwise with a mixture of (5-fluoro-2-methylindol-1-yl)acetic acid methyl ester (0.1 g), 3-(4-fluorobenzenesulfonyl)thiophene-2-carbaldehyde (0.15 g) and 1,2-dichloroethane (3.0 mL), and the resulting mixture was stirred at −10° C. for 15 minutes and then at room temperature overnight. The mixture was diluted with dichloromethane, washed with saturated aqueous sodium hydrogen carbonate solution and dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel, eluting with a mixture of cyclohexane and dichloromethane (1:1 to 0:1 by volume) to afford the title compound as a colourless gum (0.17 g).

Workup

  1. customat room temperature
  2. customovernight
  3. washwashed with saturated aqueous sodium hydrogen carbonate solution
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe residue purified by column chromatography on silica gel
  7. washeluting with a mixture of cyclohexane and dichloromethane (1:1 to 0:1 by volume)

Sources & evidence

ORD record
ord-42f6ca9cd7594bfb9478d1c37ecb500c
Source dataset
uspto-grants-2013_03
Patent number
US08394836B2

Reaction notes

Loading…