1,1-Dichloroethane → [3-(3-Benzenesulfonylthiophen-2-ylmethyl)-5-chloro-2-methylindol-1-yl]acetic acid methyl ester

HRID 1944454Notes

Reaction equation

HRID 1944454 reaction equation
C([SiH](CC)CC)C.FC(F)(F)C(O)=O.ClC(Cl)C.[CH3:19][O:20][C:21](=[O:34])[CH2:22][N:23]1[C:31]2[C:26](=[CH:27][C:28]([Cl:32])=[CH:29][CH:30]=2)[CH:25]=[C:24]1[CH3:33].[C:35]1([S:41]([C:44]2[CH:48]=[CH:47][S:46][C:45]=2[CH:49]=O)(=[O:43])=[O:42])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C(=O)([O-])O.[Na+]>[CH3:19][O:20][C:21](=[O:34])[CH2:22][N:23]1[C:31]2[C:26](=[CH:27][C:28]([Cl:32])=[CH:29][CH:30]=2)[C:25]([CH2:49][C:45]2[S:46][CH:47]=[CH:48][C:44]=2[S:41]([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)(=[O:43])=[O:42])=[C:24]1[CH3:33]

Participants

7

Reactant 5

HCID 63651,1-Dichloroethane2×HCID 6422Trifluoroacetic acid2×HCID 12052Triethylsilane2×HCID 9162623-Benzenesulfonylthiophene-2-carbaldehydeHCID 60074868Methyl 2-(5-chloro-2-methyl-1H-indol-1-yl)acetate

Product 1

HCID 67044072[3-(3-Benzenesulfonylthiophen-2-ylmethyl)-5-chloro-2-methylindol-1-yl]acetic acid methyl esterYield 76.6%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of triethylsilane (2.7 g), trifluoroacetic acid (1.6 g) and dichloroethane (8.0 mL) at −20° C. was treated dropwise with a mixture of (5-chloro-2-methylindol-1-yl)acetic acid methyl ester (0.36 g), 3-phenylsulphony-2-thiophenealdehyde (0.39 g) and dichloroethane (8.0 mL), and the resulting mixture was warmed to room temperature over a period of 1.5 hours. The mixture was treated with additional triethylsilane (2.7 g) and trifluoroacetic acid (1.6 g) and then stirred at room temperature for 1 hour. The mixture was diluted with saturated aqueous sodium hydrogen carbonate solution and extracted with dichloromethane. The combined organic extract was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a mixture of dichloromethane and ethyl acetate (1:0 to 0:1 by volume) to afford the title compound (0.55 g).

Workup

  1. extractionextracted with dichloromethane
  2. extractionThe combined organic extract
  3. washwas washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel
  7. washeluting with a mixture of dichloromethane and ethyl acetate (1:0 to 0:1 by volume)

Sources & evidence

ORD record
ord-2f9363e2d6da42bbb4a34113abcb8edb
Source dataset
uspto-grants-2013_03
Patent number
US08394836B2

Reaction notes

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