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

HRID 1944435Notes

Reaction equation

HRID 1944435 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].[N:31]1[CH:36]=[CH:35][CH:34]=[C:33]([S:37]([C:40]2[CH:44]=[CH:43][S:42][C:41]=2[CH:45]=O)(=[O:39])=[O:38])[CH:32]=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]([CH2:45][C:41]2[S:42][CH:43]=[CH:44][C:40]=2[S:37]([C:33]2[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=2)(=[O:39])=[O:38])=[C:20]1[CH3:29]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 12052Triethylsilane2×HCID 58247161Methyl 2-(5-fluoro-2-methyl-1H-indol-1-yl)acetateHCID 866521933-(Pyridine-3-sulfonyl)thiophene-2-carbaldehyde

Product 1

HCID 67044320{5-Fluoro-3-[3-(pyridine-3-sulfonyl)thiophen-2-ylmethyl]-2-methylindol-1-yl}acetic acid methyl esterYield 23.7%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A mixture of triethylsilane (0.42 g), trifluoroacetic acid (0.25 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 (0.055 g), 3-(pyridine-3-sulfonyl)thiophene-2-carbaldehyde (0.075 g) and 1,2-dichloroethane (2.0 mL), and the resulting mixture was stirred at room temperature for 20 hours. The mixture was treated with additional triethylsilane (0.42 g) and trifluoroacetic acid (0.25 g), and stirred at room temperature for 3 hours and then at 50° C. for 20 hours. 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 diethyl ether and ethyl acetate (1:0 to 0:1 by volume), followed by trituration with diethyl ether to afford the title compound as a white solid (0.027 g).

Workup

  1. stirringstirred at room temperature for 3 hours
  2. waitat 50° C. for 20 hours
  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 diethyl ether and ethyl acetate (1:0 to 0:1 by volume)

Sources & evidence

ORD record
ord-6f72a6de34ca4dab8848f040e7a9950c
Source dataset
uspto-grants-2013_03
Patent number
US08394836B2

Reaction notes

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