Thioanisole → HCID 67119187, compound

HRID 1189037Notes

Reaction equation

HRID 1189037 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:75]([O:78][CH3:79])[O:76][CH3:77])[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][C:59]1[CH:64]=[CH:63][C:62]([S:65]([CH3:68])(=[O:67])=[O:66])=[CH:61][CH:60]=1)=[CH:53][C:52]=2[O:69][CH:70]([CH3:74])[CH2:71][O:72][CH3:73])=O)C1C=CC=CC=1.C1(SC)C=CC=CC=1>C(#N)C>[CH3:77][O:76][CH:75]([O:78][CH3:79])[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][C:59]2[CH:60]=[CH:61][C:62]([S:65]([CH3:68])(=[O:66])=[O:67])=[CH:63][CH:64]=2)=[CH:53][C:52]=3[O:69][CH:70]([CH3:74])[CH2:71][O:72][CH3:73])=[N:46][CH2:45]1

Participants

6

Reactant 4

HCID 7520ThioanisoleHCID 13097Triphenylphosphine OxideHCID 67749Trifluoromethanesulfonic anhydrideHCID 66897975HCID 66897975, compound

Product 1

HCID 67119187HCID 67119187, compoundYield 10.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
4 °C

Procedure

To an ice-cooled and stirred solution of triphenylphosphine oxide (0.43 g) in acetonitrile (8 mL) was added trifluoromethanesulfonic anhydride (0.13 mL), and the mixture was stirred at 4° C. for 30 min, followed by an addition of a solution of N-[2-(benzylsulfanyl)-3,3-dimethoxypropyl]-7-(2-methoxy-1-methylethoxy)-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxamide (0.25 g) and thioanisole (0.093 mL) in acetonitrile (5 mL). After stirring at 4° C. for 30 min, the reaction mixture was partitioned between ethyl acetate and aqueous sodium hydrogen carbonate solution, and the organic layer was washed with brine, dried (MgSO4), filtered, and concentrated. The resulting precipitate was removed by filtration and washed with ethyl acetate-hexane. The combined filtrate and washings were concentrated and the residue was purified by basic silica gel chromatography (ethyl acetate:hexane=25:75 to 35:65, volume ratio) and then by silica gel chromatography (ethyl acetate:hexane=25:75 to 80:20) to give a colorless oil, which was crystallized from diethyl ether-hexane to give the title compound (21 mg, 10%) as colorless crystals. MS 535 (MH+). mp 109-112° C.

Workup

  1. stirringAfter stirring at 4° C. for 30 min
  2. customthe reaction mixture was partitioned between ethyl acetate and aqueous sodium hydrogen carbonate solution
  3. washthe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting precipitate was removed by filtration
  8. washwashed with ethyl acetate-hexane
  9. concentrationThe combined filtrate and washings were concentrated
  10. customthe residue was purified by basic silica gel chromatography (ethyl acetate:hexane=25:75 to 35:65, volume ratio)
  11. customby silica gel chromatography (ethyl acetate:hexane=25:75 to 80:20) to give a colorless oil, which
  12. customwas crystallized from diethyl ether-hexane

Sources & evidence

ORD record
ord-b55fbaa377f940a887f63fec1a16f57f
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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