1,1-Dichloroethane → {5-Fluoro-2-methyl-3-[2-(pyrimidine-5-sulfonyl)benzyl]indol-1-yl}acetic acid methyl ester

HRID 1944466Notes

Reaction equation

HRID 1944466 reaction equation
[CH3:1][O:2][C:3](=[O:16])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10](Cl)=[CH:11][CH:12]=2)[CH:7]=[C:6]1[CH3:15].[N:17]1[CH:22]=[C:21]([S:23]([C:26]2[CH:33]=[CH:32][CH:31]=[CH:30][C:27]=2[CH:28]=O)(=[O:25])=[O:24])[CH:20]=[N:19][CH:18]=1.ClC(Cl)C.C([SiH](CC)CC)C.[F:45]C(F)(F)C(O)=O>C(=O)([O-])O.[Na+]>[CH3:1][O:2][C:3](=[O:16])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([F:45])=[CH:11][CH:12]=2)[C:7]([CH2:28][C:27]2[CH:30]=[CH:31][CH:32]=[CH:33][C:26]=2[S:23]([C:21]2[CH:22]=[N:17][CH:18]=[N:19][CH:20]=2)(=[O:25])=[O:24])=[C:6]1[CH3:15]

Participants

7

Reactant 5

HCID 63651,1-DichloroethaneHCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 60074868Methyl 2-(5-chloro-2-methyl-1H-indol-1-yl)acetateHCID 866522002-(Pyrimidine-5-sulfonyl)benzaldehyde

Product 1

HCID 67044321{5-Fluoro-2-methyl-3-[2-(pyrimidine-5-sulfonyl)benzyl]indol-1-yl}acetic acid methyl esterYield 18.8%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
-70 °C

Procedure

A mixture of (5-chloro-2-methylindol-1-yl)acetic acid methyl ester (0.50 g), 2-(pyrimidine-5-sulfonyl)benzaldehyde (0.35 g) and dichloroethane (50 mL) at −70° C. was treated sequentially with triethylsilane (2.5 g) and trifluoroacetic acid (0.81 g), and the resulting mixture was stirred at −70° C. for 1 hour. The mixture was slowly warmed to room temperature and stirred at this temperature for 18 hours. The mixture was diluted with saturated aqueous sodium hydrogen carbonate solution and the phases were separated. The organic phase was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (4:1 to 2:3 by volume) to afford the title compound as a brown oil (0.12 g).

Workup

  1. temperatureThe mixture was slowly warmed to room temperature
  2. stirringstirred at this temperature for 18 hours
  3. customthe phases were separated
  4. concentrationThe organic phase was concentrated under reduced pressure
  5. customthe residue was purified by column chromatography on silica gel
  6. washeluting with a mixture of cyclohexane and ethyl acetate (4:1 to 2:3 by volume)

Sources & evidence

ORD record
ord-d3e0009280754e368c8e93bcee6923e9
Source dataset
uspto-grants-2013_03
Patent number
US08394836B2

Reaction notes

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