Thioanisole → HCID 59303546, compound

HRID 1960579Notes

Reaction equation

HRID 1960579 reaction equation
C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C([S:43][CH:44]([CH:77]([O:80][CH3:81])[O:78][CH3:79])[CH2:45][NH:46][C:47]([C:49]1[NH:50][C:51]2[C:56]([CH:57]=1)=[CH:55][C:54]([O:58][CH2:59][CH2:60][CH2:61][S:62]([CH3:65])(=[O:64])=[O:63])=[CH:53][C:52]=2[N:66]([CH3:76])[S:67]([C:70]1[CH:75]=[CH:74][CH:73]=[CH:72][N:71]=1)(=[O:69])=[O:68])=O)C1C=CC=CC=1.C1(SC)C=CC=CC=1>ClCCl.C(OCC)(=O)C>[CH3:79][O:78][CH:77]([O:80][CH3:81])[CH:44]1[S:43][C:47]([C:49]2[NH:50][C:51]3[C:56]([CH:57]=2)=[CH:55][C:54]([O:58][CH2:59][CH2:60][CH2:61][S:62]([CH3:65])(=[O:64])=[O:63])=[CH:53][C:52]=3[N:66]([CH3:76])[S:67]([C:70]2[CH:75]=[CH:74][CH:73]=[CH:72][N:71]=2)(=[O:69])=[O:68])=[N:46][CH2:45]1

Participants

7

Reactant 4

HCID 7520ThioanisoleHCID 13097Triphenylphosphine OxideHCID 67749Trifluoromethanesulfonic anhydrideHCID 59303536HCID 59303536, compound

Product 1

HCID 59303546HCID 59303546, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of triphenylphosphine oxide (1.17 g), trifluoromethanesulfonic anhydride (1.18 g) and dichloromethane (30 mL) was stirred for 15 min under ice-cooling. A solution of N-[2-(benzylthio)-3,3-dimethoxypropyl]-7-[methyl(pyridin-2-ylsulfonyl)amino]-5-[3-(methylsulfonyl)propoxy]-1H-indole-2-carboxamide (2.65 g) and thioanisole (940 mg) in dichloromethane (10 mL) was added dropwise to the reaction mixture under ice-cooling, and the mixture was stirred for 30 min under ice-cooling. The reaction mixture was diluted with ethyl acetate, and extracted with 3N hydrochloric acid. The aqueous layer was alkalified with 2N aqueous sodium hydroxide solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4), and concentrated. The obtained residue was subjected to silica gel column chromatography, and eluted with hexane-ethyl acetate (2:8-1:9, volume ratio) to give the title compound (840 mg, yield 38%) as a colorless amorphous solid.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringthe mixture was stirred for 30 min under ice-
  4. temperaturecooling
  5. extractionextracted with 3N hydrochloric acid
  6. extractionextracted with ethyl acetate
  7. washThe ethyl acetate layer was washed with saturated brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. washeluted with hexane-ethyl acetate (2:8-1:9, volume ratio)

Sources & evidence

ORD record
ord-1d3170dc63fb4c42acf8bc4dd72d24ad
Source dataset
uspto-grants-2013_04
Patent number
US08410087B2

Reaction notes

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