Hydrochloric Acid → ethyl 7-[(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indole-2-carboxylate

HRID 1851561Notes

Reaction equation

HRID 1851561 reaction equation
COC[N:4]1[C:12]2[C:7](=[CH:8][C:9]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:10][C:11]=2[NH:13][S:14]([C:17]2[S:18][CH:19]=[CH:20][CH:21]=2)(=[O:16])=[O:15])[CH:6]=[C:5]1[C:27]([O:29][CH2:30][CH3:31])=[O:28].Cl.C(O)C>C(OCC)(=O)C>[S:18]1[CH:19]=[CH:20][CH:21]=[C:17]1[S:14]([NH:13][C:11]1[CH:10]=[C:9]([O:22][C:23]([F:25])([F:26])[F:24])[CH:8]=[C:7]2[C:12]=1[NH:4][C:5]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:6]2)(=[O:15])=[O:16]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 702EthanolHCID 57901669ethyl 1-(methoxymethyl)-7-[(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indole-2-carboxylate

Product 1

HCID 57476185ethyl 7-[(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indole-2-carboxylateYield 43%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixed solution of ethyl 1-(methoxymethyl)-7-[(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indole-2-carboxylate (105 mg), 6N hydrochloric acid (4 mL) and ethanol (4 mL) was stirred at 80° C. for 3 hr. The reaction solution was diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained colorless crystals were suspended in dichloromethane (10 mL), and thionyl chloride (0.20 mL) and N,N-dimethylformamide (1 drop) were added. The mixture was stirred at 50° C. for 2 hr. Ethanol (2 mL) and triethylamine (1 mL) were added to the reaction solution, and the mixture was stirred at 50° C. for 2 hr. The reaction solution was concentrated under reduced pressure. The obtained residue was diluted with ethyl acetate, washed with aqueous citric acid solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (ethyl acetate:hexane=1:9-2:8), and the obtained oil was crystallized from diethyl ether-hexane to give the title compound (41 mg, yield 43%) as colorless crystals. melting point 192-193° C.

Workup

  1. washwashed with water and saturated brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. additionthionyl chloride (0.20 mL) and N,N-dimethylformamide (1 drop) were added
  5. additionEthanol (2 mL) and triethylamine (1 mL) were added to the reaction solution
  6. stirringthe mixture was stirred at 50° C. for 2 hr
  7. concentrationThe reaction solution was concentrated under reduced pressure
  8. additionThe obtained residue was diluted with ethyl acetate
  9. washwashed with aqueous citric acid solution and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customthe obtained oil was crystallized from diethyl ether-hexane

Sources & evidence

ORD record
ord-b228ba6814e8471380a4cb5f4f5c5709
Source dataset
uspto-grants-2015_02
Patent number
US08957070B2

Reaction notes

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