Thioanisole → 2-[5-(dimethoxymethyl)-4,5-dihydro-1,3-thiazol-2-yl]-5-(2-methoxyethoxy)-7-nitro-1H-indole

HRID 2239016Notes

Reaction equation

HRID 2239016 reaction equation
C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C([S:41][CH:42]([CH:64]([O:67][CH3:68])[O:65][CH3:66])[CH2:43][NH:44][C:45]([C:47]1[NH:48][C:49]2[C:54]([CH:55]=1)=[CH:53][C:52]([O:56][CH2:57][CH2:58][O:59][CH3:60])=[CH:51][C:50]=2[N+:61]([O-:63])=[O:62])=O)C1C=CC=CC=1.C1(SC)C=CC=CC=1>ClCCl.CCCCCC.C(OCC)(=O)C.O>[CH3:66][O:65][CH:64]([O:67][CH3:68])[CH:42]1[S:41][C:45]([C:47]2[NH:48][C:49]3[C:54]([CH:55]=2)=[CH:53][C:52]([O:56][CH2:57][CH2:58][O:59][CH3:60])=[CH:51][C:50]=3[N+:61]([O-:63])=[O:62])=[N:44][CH2:43]1

Participants

9

Reactant 4

HCID 7520ThioanisoleHCID 9845Trifluoroacetic anhydrideHCID 13097Triphenylphosphine OxideHCID 59136022N-[2-(benzylthio)-3,3-dimethoxypropyl]-5-(2-methoxyethoxy)-7-nitro-1H-indole-2-carboxamide

Product 1

HCID 574762212-[5-(dimethoxymethyl)-4,5-dihydro-1,3-thiazol-2-yl]-5-(2-methoxyethoxy)-7-nitro-1H-indoleYield 173.2%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Triphenylphosphine oxide (3 g) was dissolved in dichloromethane (30 mL), trifluoroacetic anhydride (3.1 g) was added under ice-cooling, and the mixture was stirred for 10 min. A solution of N-[2-(benzylthio)-3,3-dimethoxypropyl]-5-(2-methoxyethoxy)-7-nitro-1H-indole-2-carboxamide (5.0 g) and thioanisole (2.5 g) in dichloromethane (20 mL) was added dropwise to this suspension under ice-cooling. The reaction solution was allowed to warm to room temperature, and stirred for 10 min. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and filtrated, and the filtrate was concentrated under reduced pressure. The obtained crude product was subjected to silica gel column chromatography (ethyl acetate:hexane=10:90-40:60), and the obtained solid was washed with ethyl acetate-hexane to give the title compound (6.8 g, yield 97%) as yellow crystals. melting point 100-101° C.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringstirred for 10 min
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltrated
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe obtained crude product
  10. washthe obtained solid was washed with ethyl acetate-hexane

Sources & evidence

ORD record
ord-22ec8edcdc254ddeb47dca8f4872fc6b
Source dataset
uspto-grants-2010_05
Patent number
US07718798B2

Reaction notes

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