1-Phenyl-1-propanone → (Z)-4-(1-(6-chloropyridin-3-yl)-2-phenylbut-1-enyl)phenol

HRID 626095Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 626095
[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)(=O)[CH2:2][CH3:3].[Cl:11][C:12]1[N:17]=[CH:16][C:15]([C:18]([C:20]2[CH:25]=[CH:24][C:23]([O:26]C3CCCCO3)=[CH:22][CH:21]=2)=O)=[CH:14][CH:13]=1>C1COCC1.[Zn].Cl[Ti](Cl)(Cl)Cl>[Cl:11][C:12]1[N:17]=[CH:16][C:15](/[C:18](/[C:20]2[CH:21]=[CH:22][C:23]([OH:26])=[CH:24][CH:25]=2)=[C:1](\[C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)/[CH2:2][CH3:3])=[CH:14][CH:13]=1

Komponenten

6

Edukt 2

HCID 71481-Phenyl-1-propanoneHCID 89655790(6-chloropyridin-3-yl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)methanone

Produkt 1

HCID 71617026(Z)-4-(1-(6-chloropyridin-3-yl)-2-phenylbut-1-enyl)phenolAusbeute 41 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23994ZincKatalysatorHCID 24193Titanium TetrachlorideKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a stirred mixture of Zn powder (8.06 g, 6 eq) in dry THF at rt under N2 was slowly added TiCl4 (6.8 mL, 3 eq). The resulting mixture was heated to 80° C. and refluxed for 1 h. After cooling to rt, a mixture of propiophenone (8.2 g, 3.0 eq) and (6-chloropyridin-3-yl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)methanone (6.5 g, 1.0 eq) in dry THF was added. The resulting mixture was refluxed for additional 2 h, then quenched with saturated aq. Na2CO3 solution, extracted with EtOAc. The extract was dried, concentrated, and purified by column chromatography to give a Z/E mixture of the product (6.3 g, 92%, Z/E=1/1). The Z/E mixture was recrystallized in petroleum ether/CH2Cl2 to give the pure Z-isomer (2.8 g, 41% yield). 1H NMR (400 MHz, CDCl3) δ 7.85 (s, 1H), 7.06-7.25 (m, 8H), 6.97 (d, J=8.4 Hz, 1H), 6.83 (d, J=8.0 Hz, 2H), 2.51 (q, J=7.6 Hz, 2H), 0.94 (t, J=7.6 Hz, 3H); m/z=336 [M+1]+.

Aufarbeitung

  1. temperaturerefluxed for 1 h
  2. temperatureAfter cooling to rt
  3. additionwas added
  4. temperatureThe resulting mixture was refluxed for additional 2 h
  5. customquenched with saturated aq. Na2CO3 solution
  6. extractionextracted with EtOAc
  7. customThe extract was dried
  8. concentrationconcentrated
  9. custompurified by column chromatography
  10. customto give
  11. additiona Z/E mixture of the product (6.3 g, 92%, Z/E=1/1)
  12. customThe Z/E mixture was recrystallized in petroleum ether/CH2Cl2
  13. customto give the pure Z-isomer (2.8 g, 41% yield)

Quellen und Nachweise

ORD-Eintrag
ord-4ac3f2a4ecc64ab8aecc90f976850eb1
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09309211B2

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