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

HRID 1944432

Reaction equation

HRID 1944432 reaction equation
C([SiH](CC)CC)C.FC(F)(F)C(O)=O.[C:15]1([S:21]([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][C:25]=2[CH:30]=O)(=[O:23])=[O:22])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[CH3:32][O:33][C:34](=[O:47])[CH2:35][N:36]1[C:44]2[C:39](=[CH:40][C:41]([F:45])=[CH:42][CH:43]=2)[CH:38]=[C:37]1[CH3:46]>ClCCl.ClCCCl>[CH3:32][O:33][C:34](=[O:47])[CH2:35][N:36]1[C:44]2[C:39](=[CH:40][C:41]([F:45])=[CH:42][CH:43]=2)[C:38]([CH2:30][C:25]2[CH:26]=[N:27][CH:28]=[CH:29][C:24]=2[S:21]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)(=[O:22])=[O:23])=[C:37]1[CH3:46]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 12052Triethylsilane2×HCID 58247161Methyl 2-(5-fluoro-2-methyl-1H-indol-1-yl)acetateHCID 866521924-Phenylsulfonylpyridine-3-carbaldehyde

Product 1

HCID 67044979[5-Fluoro-3-(4-phenylsulfonylpyridin-3-ylmethyl)-2-methylindol-1-yl]acetic acid methyl esterYield 14.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A mixture of triethylsilane (5.1 g), trifluoroacetic acid (3.1 g) and 1,2-dichloroethane (20 mL) at −10° C. was treated dropwise with a mixture of 4-phenylsulfonylpyridine-3-carbaldehyde (1.9 g), (5-fluoro-2-methylindol-1-yl)acetic acid methyl ester (0.66 g) and 1,2-dichloroethane (20 mL), and the resulting mixture was stirred at room temperature for 20 hours. The mixture was treated with additional triethylsilane (5.1 g) and trifluoroacetic acid (3.1 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 was purified by column chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (1:0 to 0:1 by volume), followed by trituration with diethyl ether to afford the title compound as a yellow powder (0.19 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 was purified by column chromatography on silica gel
  7. washeluting with a mixture of cyclohexane and ethyl acetate (1:0 to 0:1 by volume)

Sources & evidence

ORD record
ord-1baa32d7125a4cff83924cac7c8e3533
Source dataset
uspto-grants-2013_03
Patent number
US08394836B2

Linked notes

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