Ethanol → 2-(Benzofuran-2-carbonylamino)-4-(4-methyl-3-nitro-phenyl)thiophene-3-carboxylic acid

HRID 602840Notes

Reaction equation

HRID 602840 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].[CH3:33][C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][C:35]=1[N+:43]([O-:45])=[O:44].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:37]2[CH:38]=[CH:39][C:34]([CH3:33])=[C:35]([N+:43]([O-:45])=[O:44])[CH:36]=2)[C:17]=1[C:18]([OH:20])=[O:19])=[O:11]

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27735154-Methyl-3-nitrobenzeneboronic acidHCID 59225740Tert-butyl 2-(benzofuran-2-carbonylamino)-4-(trifluoromethylsulfonyloxy)thiophene-3-carboxylate

Product 1

HCID 595360142-(Benzofuran-2-carbonylamino)-4-(4-methyl-3-nitro-phenyl)thiophene-3-carboxylic acidYield 81.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

tert-butyl 2-(benzofuran-2-carbonylamino)-4-(trifluoromethylsulfonyloxy)thiophene-3-carboxylate (82, 50 mg, 0.102 mmol), 4-methyl-3-nitrophenylboronic acid (28 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, triturated in methanol, centrifuged, decanted and the resulting solid was dried under vacuum and 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 84 as a white powder (35.2 mg, 43%). 1H NMR (500 MHz, DMSO d6) δ=13.48 (br, 1H), 12.57 (br, 1H), 7.96 (s, 1H), 7.86 (m, 2H), 7.76 (d, 1H), 7.64 (d, 1H), 7.57 (t, 1H), 7.49 (d, 1H), 7.42 (t, 1H), 2.55 (s, 3H) ppm.

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. customtriturated in methanol
  8. customdecanted
  9. customthe resulting solid was dried under vacuum
  10. additiontreated with a 1:1 mixture of methylene chloride and trifluoroacetic acid
  11. concentrationAfter 4 hours the mixture was concentrated in vacuo
  12. customthe residue triturated in methylene chloride
  13. customdecanted
  14. customdried under high vacuum

Sources & evidence

ORD record
ord-989e8cf48e294973ab38aa6a560e7574
Source dataset
uspto-grants-2011_03
Patent number
US07906553B2

Reaction notes

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