Toluene → Methyl 5-[1,1′-biphenyl]-4-yl-2-thiophenecarboxylate

HRID 1892084Notes

Reaction equation

HRID 1892084 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[CH:4][CH:3]=1.[C:11]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+].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.O.C(O)C>[C:11]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:16]=[CH:15][C:14]([C:2]2[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[CH:4][CH:3]=2)=[CH:13][CH:12]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 1512531,1'-Biphenyl-4-yl-boronic acidHCID 605713Methyl 5-bromothiophene-2-carboxylate

Product 1

HCID 12317965Methyl 5-[1,1′-biphenyl]-4-yl-2-thiophenecarboxylateYield 75.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixture of compound 1021 (5.0 g, 22.6 mmol), biphenyl-4-ylboronic acid (5.4 g, 27.1 mmol), sodium carbonate (5.9 g, 56.5 mmol), tetrakis(triphenylphosphine)palladium(0) (2.65 g, 2.3 mmol), toluene (200 mL), ethanol (100 mL) and water (50 mL) was heated to reflux for 12 hours under nitrogen atmosphere. The reaction mixture was cooled to ambient temperature, and extracted with dichloromethane (2×250 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by flash chromatography with silica gel (5% EtOAc in hexane) to give compound 1022 (5.0 g). 1H NMR (CDCl3, 300 MHz) δ 3.92 (s, 3H), 7.32-7.49 (m, 4H), 7.62-7.80 (m, 7H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 12 hours under nitrogen atmosphere
  3. extractionextracted with dichloromethane (2×250 mL)
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by flash chromatography with silica gel (5% EtOAc in hexane)

Sources & evidence

ORD record
ord-82caae39f2b942b092f05e988f10f05f
Source dataset
uspto-grants-2013_08
Patent number
US08507647B2

Reaction notes

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