Pivalic acid → (E)-tert-butyl 3-(4-((6-methoxy-2-(4-(trifluoromethyl)phenyl)benzo[b]thiophen-3 yl)oxy)phenyl)acrylate

HRID 632629Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 632629
[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][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[CH:14][CH:13]=3)=[CH:9][S:8][C:7]=2[CH:27]=1.Br[C:29]1[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=1.CC(C)(C)C(O)=O.C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O>[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][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])=[CH:14][CH:13]=3)=[C:9]([C:29]3[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=3)[S:8][C:7]=2[CH:27]=1

Komponenten

6

Edukt 4

HCID 6417Pivalic acidHCID 11430Potassium CarbonateHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 86730640(E)-tert-butyl 3-(4-((6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate

Produkt 1

HCID 86730641(E)-tert-butyl 3-(4-((6-methoxy-2-(4-(trifluoromethyl)phenyl)benzo[b]thiophen-3 yl)oxy)phenyl)acrylateAusbeute 86 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

To a 5 mL microwave vial, added a solution of (E)-tert-butyl 3-(4-((6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate (50 mg, 0.13 mmol) in anhydrous DMA (1.5 mL), followed by 1-bromo-4-(trifluoromethyl)benzene (35.3 mg, 0.16 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, 10.4 mg, 0.013 mmol), trimethylacetic acid (40.1 mg, 0.392 mmol) and potassium carbonate (54.2 mg, 0.392 mmol). The microwave vial was scaled, 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 and brine. The combined organic layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo to give a red brown residue which was purified by column chromatography (SiO2, 0-30% EtOAc/heptane) to afford (E)-tert-butyl 3-(4-((6-methoxy-2-(4-(trifluoromethyl)phenyl)benzo[b]thiophen-3 yl)oxy)phenyl)acrylate (59.4 mg, 0.11 mmol, 86% yield). 1H NMR (400 MHz, CD3OD) δ ppm=1.42-1.61 (m, 9 H), 3.77-3.98 (m, 3 H), 6.31 (d, J=15.66 Hz, 1 H), 6.87-7.04 (m, 3 H), 7.28 (d, J=9.09 Hz, 1 H), 7.46 (d, J=2.53 Hz, 1 H), 7.47-7.57 (m, 3 H), 7.65 (d, J=8.08 Hz, 2 H), 7.89 (d, J=8.08 Hz, 2 H), LC/MS (m/z, MH+): 471.40.

Aufarbeitung

  1. custompurged
  2. additionback-filled with nitrogen
  3. customirradiation for 2 h at 150° C
  4. additionUpon completion the reaction was diluted with EtOAc
  5. washwashed with water and brine
  6. dry with materialThe combined organic layer was dried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a red brown residue which
  10. customwas purified by column chromatography (SiO2, 0-30% EtOAc/heptane)

Quellen und Nachweise

ORD-Eintrag
ord-7def578f646f478795049c1c16c41766
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09321746B2

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