(4-Fluoro-2-methylphenyl)boronic acid → 3-(4-Methylthiophenyl)-4-(2-methyl-4-fluorophenyl)thiophene

HRID 2298122Notes

Reaction equation

HRID 2298122 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)=[CH:13][S:14][CH:15]=2)=[CH:7][CH:6]=1)(=O)=O.[CH3:23]C1C=C(F)C=CC=1B(O)O>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].C(O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][S:2][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=3[CH3:23])=[CH:13][S:14][CH:15]=2)=[CH:7][CH:6]=1

Participants

7

Reactant 2

HCID 2734665(4-Fluoro-2-methylphenyl)boronic acidHCID 104268843-(4-Methylsulfonylphenyl)-4-(4-fluorophenyl)thiophene

Product 1

HCID 545620343-(4-Methylthiophenyl)-4-(2-methyl-4-fluorophenyl)thiopheneYield 74.2%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 10340Sodium CarbonateSolvent

Procedure

The mono-substituted thiophene from Example 14 (1.8 mmol, 520 mg) was combined with the 2-methyl-4-fluorophenyl boronic acid (2 eq, 3.6 mmol, 562 mg) in 8.0 ml of toluene, 4.3 ml of 2 M sodium carbonate, 10 ml of ethanol and tetrakis(triphenylphosphine)-palladium(0) (1.0 g) and was stirred at reflux overnight. The reaction was concentrated in vacuo and the residue was partitioned between toluene and water. The toluene layer was dried (MgSO4) and reconcentrated in vacuo. The residue was purified via silica chromatography (Waters, LC-2000) in 97% hexane/ethyl acetate to give 3-(4-methylthiophenyl)-4-(2-methyl-4-fluorophenyl)thiophene (420 mg) as a semi-solid, NMR (CDCl3) δ 1.90(s, 3H), 2.43(s, 3H), 6.8-6.9(m, 2H), 7.05(q, J=8 Hz, 4H), 7.12-7.18(m, 2H), 7.33(d, J=2 Hz, 1H).

Workup

  1. temperatureat reflux overnight
  2. concentrationThe reaction was concentrated in vacuo
  3. customthe residue was partitioned between toluene and water
  4. dry with materialThe toluene layer was dried (MgSO4)
  5. customThe residue was purified via silica chromatography (Waters, LC-2000) in 97% hexane/ethyl acetate

Sources & evidence

ORD record
ord-debf4b3ddf21493ca89c656688c09c20
Source dataset
uspto-grants-2002_12
Patent number
US06492413B2

Reaction notes

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