Ethanol → Methyl 5-(4-methoxyphenyl)-4-methyl-3-(4-sulfamoylphenyl)thiophene-2-carboxylate

HRID 1053257Notes

Reaction equation

HRID 1053257 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[C:4]([C:11]2[CH:16]=[CH:15][C:14]([S:17](=[O:20])(=[O:19])[NH2:18])=[CH:13][CH:12]=2)[C:3]=1[CH3:21].C(O)C.[CH3:25][O:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.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>[CH3:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([C:2]2[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[C:4]([C:11]3[CH:16]=[CH:15][C:14]([S:17](=[O:20])(=[O:19])[NH2:18])=[CH:13][CH:12]=3)[C:3]=2[CH3:21])=[CH:29][CH:28]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 68285968Methyl 5-bromo-4-methyl-3-(4-sulfamoylphenyl)thiophene-2-carboxylate2×

Product 1

HCID 68285228Methyl 5-(4-methoxyphenyl)-4-methyl-3-(4-sulfamoylphenyl)thiophene-2-carboxylateYield 83.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
97.5 °C

Procedure

To the solution of methyl 5-bromo-4-methyl-3-(4-sulfamoylphenyl)thiophene-2-carboxylate (compound 7c, 3.0 g, 7.69 mmol) in a mixture of toluene: ethanol (25:75 ml) was added (4-methoxyphenyl)boronic acid (1.28 g, 8.46 mmol) and potassium carbonate (3.18 g, 23.07 mmol) at 25° C. Nitrogen gas was bubbled through reaction mixture for 15 minutes. To this was added tetrakis(triphenylphosphine)palladium(0) (0.487 g, 0.422 mmol) under nitrogen and reaction mixture was heated at 95-100° C. for 1 hr under stirring. The progress of reaction was monitored by TLC. The reaction mixture was cooled to 25° C. and filtered through celite, and then washed with ethyl acetate (50 ml). The filtrate was concentrated under reduced pressure to obtain a crude product, that was then purified by column chromatography over silica gel (100-200 mesh) using 50% ethyl acetate in hexanes as an eluent to obtain the title compound (20% ethyl ester as trans esterified product was observed) (2.69 g, 84%).

Workup

  1. customNitrogen gas was bubbled through reaction mixture for 15 minutes
  2. customreaction mixture
  3. customThe progress of reaction
  4. temperatureThe reaction mixture was cooled to 25° C.
  5. filtrationfiltered through celite
  6. washwashed with ethyl acetate (50 ml)
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customto obtain a crude product, that
  9. customwas then purified by column chromatography over silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-1bab4fa773f24b7698478dd19ef0a23a
Source dataset
uspto-grants-2016_07
Patent number
US09393247B2

Reaction notes

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