Ethanol → 2-(Benzofuran-2-carbonylamino)-4-[4-(trifluoromethoxy)phenyl]thiophene-3-carboxylic acid

HRID 602841Notes

Reaction equation

HRID 602841 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]([NH:12][C:13]1[S:14][CH:15]=[C:16](OS(C(F)(F)F)(=O)=O)[C:17]=1[C:18]([O:20]C(C)(C)C)=[O:19])=[O:11].[F:33][C:34]([F:46])([F:45])[O:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1.C(=O)([O-])[O-].[Na+].[Na+].C(O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C1(C)C=CC=CC=1>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]([NH:12][C:13]1[S:14][CH:15]=[C:16]([C:39]2[CH:38]=[CH:37][C:36]([O:35][C:34]([F:33])([F:45])[F:46])=[CH:41][CH:40]=2)[C:17]=1[C:18]([OH:20])=[O:19])=[O:11]

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27343864-(Trifluoromethoxy)phenylboronic acidHCID 59225740Tert-butyl 2-(benzofuran-2-carbonylamino)-4-(trifluoromethylsulfonyloxy)thiophene-3-carboxylate

Product 1

HCID 595360402-(Benzofuran-2-carbonylamino)-4-[4-(trifluoromethoxy)phenyl]thiophene-3-carboxylic acidYield 25%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

tert-butyl 2-(benzofuran-2-carbonylamino)-4-(trifluoromethylsulfonyloxy)thiophene-3-carboxylate (85, 50 mg, 0.102 mmol), 4-(trifluoromethoxy)phenylboronic acid (32 mg, 0.153 mmol), Tetrakis(triphenylphosphine)palladium(0) (1.0 mg, 0.001 mmol), and sodium carbonate (42 mg, 0.407 mmol), were combined in 2:1:1 ethanol, toluene and water the biphasic mixture was stirred vigorously in sealed vial at 70 C. After 2 hours, the mixture was filtered through Celite and the Celite rinsed with methylene chloride. The organic fraction of the filtrate was washed with water, dried with sodium sulfate, filtered, concentrated, purified by preparative layer chromatography (10% ethyl acetate/Hexane) then treated with a 1:1 mixture of methylene chloride and trifluoroacetic acid. After 4 hours the mixture was concentrated in vacuo, and the residue triturated in methylene chloride, centrifuged, decanted and dried under high vacuum to give 87 as a white powder (11.1 mg, 25%). 1H NMR (500 MHz, DMSO d6) δ=13.35 (br, 1H), 12.55 (br, 1H), 7.87 (d, 1H), 7.86 (s, 1H), 7.76 (d, 1H), 7.57 (t, 1H), 7.49 (d, 2H), 7.42 (t, 1H), 7.36 (d 2H), 7.08 (s, 1H) ppm. ESI MS

Workup

  1. filtrationthe mixture was filtered through Celite
  2. washthe Celite rinsed with methylene chloride
  3. washThe organic fraction of the filtrate was washed with water
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by preparative layer chromatography (10% ethyl acetate/Hexane)
  8. additionthen treated with a 1:1 mixture of methylene chloride and trifluoroacetic acid
  9. concentrationAfter 4 hours the mixture was concentrated in vacuo
  10. customthe residue triturated in methylene chloride
  11. customdecanted
  12. customdried under high vacuum

Sources & evidence

ORD record
ord-3b04cee6c25a45cf8d76bc788bf7139c
Source dataset
uspto-grants-2011_03
Patent number
US07906553B2

Reaction notes

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