Pivalic acid → (E)-4-(4-((2-(2-isopropylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)but-3-en-2-one

HRID 632666Notes

Reaction equation

HRID 632666 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([O:11][C:12]3[CH:17]=[CH:16][C:15](/[CH:18]=[CH:19]/[C:20](=[O:22])[CH3:21])=[CH:14][CH:13]=3)=[CH:9][S:8][C:7]=2[CH:23]=1.I[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[CH:31]([CH3:33])[CH3:32].CC(C)(C)C(O)=O.C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O>[CH:31]([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=1[C:9]1[S:8][C:7]2[CH:23]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=2[C:10]=1[O:11][C:12]1[CH:13]=[CH:14][C:15](/[CH:18]=[CH:19]/[C:20](=[O:22])[CH3:21])=[CH:16][CH:17]=1)([CH3:33])[CH3:32]

Participants

6

Reactant 4

HCID 6417Pivalic acidHCID 11430Potassium CarbonateHCID 87931o-IodocumeneHCID 118574934(E)-4-(4-((6-methoxybenzo [b]thiophen-3-yl)oxy)phenyl)but-3-en-2-one

Product 1

HCID 118574977(E)-4-(4-((2-(2-isopropylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)but-3-en-2-oneYield 58.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a 5 mL microwave vial, added a solution of (E)-4-(4-((6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)but-3-en-2-one (90 mg, 0.277 mmol) in anhydrous DMA (3.0 mL), followed by 1-iodo-2-isopropylbenzene (137 mg, 0.555 mmol), chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′,4′,6′-tri-i-propyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (BrettPhos Palladacycle 1st generation, 22.16 mg, 0.028 mmol), trimethylacetic acid (85 mg, 0.832 mmol) and potassium carbonate (115 mg, 0.832 mmol). The microwave vial was sealed, purged and back-filled with nitrogen. The reaction mixture subjected to microwave irradiation for 2 h at 150° C. Upon completion the reaction was diluted with EtOAc, and washed with water (2×) and brine (1×). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give the crude product, which was purified by column chromatography (SiO2, 0-20% EtOAc/heptane) to afford (E)-4-(4-((2-(2-isopropylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)but-3-en-2-one (71.3 mg, 0.161 mmol, 58% yield). LC/MS (m/z, MH+): 443.0.

Workup

  1. customThe microwave vial was sealed
  2. custompurged
  3. additionback-filled with nitrogen
  4. customirradiation for 2 h at 150° C
  5. additionUpon completion the reaction was diluted with EtOAc
  6. washwashed with water (2×) and brine (1×)
  7. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give the crude product, which
  11. customwas purified by column chromatography (SiO2, 0-20% EtOAc/heptane)

Sources & evidence

ORD record
ord-f76f3777ed0047e999c7a7ae7bf2750a
Source dataset
uspto-grants-2016_04
Patent number
US09321746B2

Reaction notes

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