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

HRID 1944497Notes

Reaction equation

HRID 1944497 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].[C:31]1([S:37]([C:40]2[N:44]([CH3:45])[CH:43]=[N:42][C:41]=2[CH:46]=O)(=[O:39])=[O:38])[CH:36]=[CH:35][CH:34]=[CH:33][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]([CH2:46][C:41]2[N:42]=[CH:43][N:44]([CH3:45])[C:40]=2[S:37]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)(=[O:38])=[O:39])=[C:20]1[CH3:29]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 58247161Methyl 2-(5-fluoro-2-methyl-1H-indol-1-yl)acetateHCID 866522145-benzenesulfonyl-1-methyl-1H-imidazole-4-carbaldehyde

Product 1

HCID 67045042[3-(5-benzenesulfonyl-1-methyl-1H-imidazol-4-ylmethyl)-5-fluoro-2-methylindol-1-yl]acetic acid methyl esterYield 59.6%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A mixture of triethylsilane (0.17 g), trifluoroacetic acid (0.10 g) and 1,2-dichloroethane (5.0 mL) at −5° C. was treated dropwise with a mixture of (5-fluoro-2-methylindol-1-yl)acetic acid methyl ester (0.022 g), 5-benzenesulfonyl-1-methyl-1H-imidazole-4-carbaldehyde (0.030 g) and 1,2-dichloroethane (3.0 mL), and the resulting mixture was stirred at room temperature overnight and then at 45° C. for 2 hours. The mixture was diluted with dichloromethane, washed with saturated aqueous sodium hydrogen carbonate solution and dried using a phase separation cartridge. The solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel, eluting with a mixture of ethyl acetate and dichloromethane (0:1 to 2:5 by volume) to afford the title compound as a yellow oil (0.027 g).

Workup

  1. waitat 45° C. for 2 hours
  2. washwashed with saturated aqueous sodium hydrogen carbonate solution
  3. customdried
  4. customa phase separation cartridge
  5. customThe solvent was removed under reduced pressure
  6. customthe residue was purified by column chromatography on silica gel
  7. washeluting with a mixture of ethyl acetate and dichloromethane (0:1 to 2:5 by volume)

Sources & evidence

ORD record
ord-a345620d4f9a4c3e89efeda8a03ab657
Source dataset
uspto-grants-2013_03
Patent number
US08394836B2

Reaction notes

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