Toluene → Methyl 4-methyl-3-(4-sulfamoylphenyl)thiophene-2-carboxylate

HRID 1053255Notes

Reaction equation

HRID 1053255 reaction equation
Br[C:2]1[C:6]([CH3:7])=[CH:5][S:4][C:3]=1[C:8]([O:10][CH3:11])=[O:9].C1(C)C=CC=CC=1.[S:19]([C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1)(=[O:22])(=[O:21])[NH2:20].C(=O)([O-])[O-].[K+].[K+]>C(O)C>[CH3:7][C:6]1[C:2]([C:26]2[CH:27]=[CH:28][C:23]([S:19](=[O:22])(=[O:21])[NH2:20])=[CH:24][CH:25]=2)=[C:3]([C:8]([O:10][CH3:11])=[O:9])[S:4][CH:5]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 2808193Methyl 3-bromo-4-methylthiophene-2-carboxylate2×HCID 223919774-(Aminosulphonyl)benzeneboronic acid

Product 1

HCID 68285465Methyl 4-methyl-3-(4-sulfamoylphenyl)thiophene-2-carboxylateYield 74.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
105 °C

Procedure

To a stirred suspension of methyl 3-bromo-4-methylthiophene-2-carboxylate (compound 7a, 9.0 g, 38.0 mmol) in ethanol: toluene (100:30 ml) in sealed tube, (4-sulfamoylphenyl)boronic acid (8.46 g, 42.0 mmol) and potassium carbonate (10.57 g, 76.0 mmol) were added under a nitrogen atmosphere at room temperature (about 25° C.). Nitrogen gas was purged to this suspension for further 15 minute at room temperature (about 25° C.) and tetrakis(triphenyl phosphine)palladium(0) (2.21 g, 1.9 mmol) was added at 25° C. and sealed tube was closed. The reaction mixture was stirred at 105° C. for 15 hr and the progress of the reaction was monitored by TLC. Reaction mixture was filtered and washed with ethyl acetate (2×100 ml). Organic layer was concentrated under reduced pressure to obtain crude product as semi-solid (11.2 g); which was 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) (8.8 g, 70.70%).

Workup

  1. additionwas added at 25° C.
  2. customsealed tube
  3. customwas closed
  4. customReaction mixture
  5. filtrationwas filtered
  6. washwashed with ethyl acetate (2×100 ml)
  7. concentrationOrganic layer was concentrated under reduced pressure
  8. customto obtain crude product as semi-solid (11.2 g)
  9. customwhich was purified by column chromatography over silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-7679a2d37b7b445598b738ad043b8db6
Source dataset
uspto-grants-2016_07
Patent number
US09393247B2

Reaction notes

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