Potassium Carbonate → Methyl 4-(4-methyl-3-thienyl)-3-(trifluoromethyl)benzoate

HRID 219794Notes

Reaction equation

HRID 219794 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13].CC1C=CC=CC=1C1C=CC(C(O)=O)=CC=1C(F)(F)F.[CH3:36][C:37]1[C:38](B(O)O)=[CH:39][S:40][CH:41]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CCOC(C)=O.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>[CH3:36][C:37]1[C:38]([C:2]2[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=2[C:12]([F:15])([F:14])[F:13])=[CH:39][S:40][CH:41]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 50839314-Methyl-3-thiopheneboronic acidHCID 10891333Methyl 4-bromo-3-(trifluoromethyl)benzoateHCID 594958132'-Methyl-2-(trifluoromethyl)-[1,1'-biphenyl]-4-carboxylic acid

Product 1

HCID 67528440Methyl 4-(4-methyl-3-thienyl)-3-(trifluoromethyl)benzoateYield 99.6%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl 4-bromo-3-(trifluoromethyl)benzoate (Intermediate 19, step 1) (3.50 g; 12.37 mmol; 1 eq.), 4-methyl-3-thiopheneboronic acid (1.93 g; 13.60 mmol; 1.10 eq.), potassium carbonate (8.54 g; 61.83 mmol; 5 eq.), tetrakis(triphenylphosphine)palladium(0) (1.43 g; 1.24 mmol; 0.10 eq.) were taken up in Toluene (17.50 mL) and water (17.50 mL) under N2 atmosphere. The reaction mixture was purged with vacuum, then degassed with N2 for 5 minutes and then refluxed for 24 hours. The reaction mixture was cooled to RT, filtered over a pad of celite and washed with toluene (200 mL). The filtrate was concentrated affording a brown oil that was taken in EtOAc (300 mL). The organic layer was washed with a saturated aqueous solution of NaHCO3 solution (100 mL), water (100 mL) and brine (100 mL), dried over MgSO4 and concentrated affording the title compound as a brown oil (3.7 g, 99%). HPLC (Method A) Rt 5.21 min (Purity: 68.1%).

Workup

  1. customThe reaction mixture was purged with vacuum
  2. customdegassed with N2 for 5 minutes
  3. temperaturerefluxed for 24 hours
  4. filtrationfiltered over a pad of celite
  5. washwashed with toluene (200 mL)
  6. concentrationThe filtrate was concentrated
  7. customaffording a brown oil that
  8. washThe organic layer was washed with a saturated aqueous solution of NaHCO3 solution (100 mL), water (100 mL) and brine (100 mL)
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-a16b3d702a094b70a8b637db3ac044cd
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

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