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Hydrochloric Acid → 6-(2,6-Dibromo-4-chloromethyl-benzyl)-4-isopropyl-pyridazin-3-one

HRID 1157250
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1157250
Cl[C:2]1[N:7]=[N:6][C:5]([CH:8]([C:11]2[C:16]([Br:17])=[CH:15][C:14]([CH2:18]OC3CCCCO3)=[CH:13][C:12]=2[Br:26])C#N)=[CH:4][C:3]=1[CH:27]([CH3:29])[CH3:28].C([O-])(=[O:32])C.[Na+].[ClH:35]>C(O)(=O)C.C(OCC)(=O)C>[Br:26][C:12]1[CH:13]=[C:14]([CH2:18][Cl:35])[CH:15]=[C:16]([Br:17])[C:11]=1[CH2:8][C:5]1[CH:4]=[C:3]([CH:27]([CH3:29])[CH3:28])[C:2](=[O:32])[NH:7][N:6]=1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 3

HCID 313Hydrochloric Acid2×HCID 517045Sodium AcetateHCID 59834544(6-Chloro-5-isopropyl-pyridazin-3-yl)-[2,6-dibromo-4-(tetrahydro-pyran-2-yloxymethyl)-phenyl]-acetonitrile

Produkt 1

HCID 598345186-(2,6-Dibromo-4-chloromethyl-benzyl)-4-isopropyl-pyridazin-3-oneAusbeute 36 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176
Acetic Acid
Lösungsmittel
2×
HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

A mixture of (6-chloro-5-isopropyl-pyridazin-3-yl)-[2,6-dibromo-4-(tetrahydro-pyran-2-yloxymethyl)-phenyl]-acetonitrile (61) (332.8 mg, 0.61 mmol) and sodium acetate (103.8 mg, 1.26 mmol) in glacial acetic acid (2.7 mL) was heated to reflux for 2.5 h. The reaction was then treated with concentrated hydrochloric acid (2.0 mL) and heated to reflux for 18 h. At this time, the reaction was treated with more concentrated hydrochloric acid (6.0 mL) and additional glacial acetic acid (3.0 mL) and heated to reflux for an additional 24 h. The reaction was then cooled to 25° C. and diluted with ethyl acetate (150 mL). This solution was washed with a saturated aqueous sodium chloride solution (2×50 mL) and a saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate, filtered, and concentrated under vacuum. The resulting brown oil was treated with glacial acetic acid (1.0 mL) and concentrated hydrochloric acid (6.0 mL) and was heated to reflux for 3 d. At this time, the reaction was cooled to 25° C. and diluted with ethyl acetate (150 mL). This solution was washed with a saturated aqueous sodium chloride solution (2×50 mL) and a saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate, filtered, and concentrated under vacuum. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 2/1 hexanes/ethyl acetate) afforded 6-(2,6-dibromo-4-chloromethyl-benzyl)-4-isopropyl-pyridazin-3-one (62) (96.3 mg, 36%) as an off-white solid; LRMS for C15H15Br2ClN2O (M+H) at m/z=433. Molecular Weight=434.5606; Exact Mass=431.9240

Aufarbeitung

  1. temperaturewas heated
  2. temperatureto reflux for 2.5 h
  3. temperatureheated
  4. temperatureto reflux for 18 h
  5. temperatureheated
  6. temperatureto reflux for an additional 24 h
  7. washThis solution was washed with a saturated aqueous sodium chloride solution (2×50 mL)
  8. dry with materiala saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum
  11. additionThe resulting brown oil was treated with glacial acetic acid (1.0 mL) and concentrated hydrochloric acid (6.0 mL)
  12. temperaturewas heated
  13. temperatureto reflux for 3 d
  14. temperatureAt this time, the reaction was cooled to 25° C.
  15. additiondiluted with ethyl acetate (150 mL)
  16. washThis solution was washed with a saturated aqueous sodium chloride solution (2×50 mL)
  17. dry with materiala saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate
  18. filtrationfiltered
  19. concentrationconcentrated under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-aa52463c9be34d2fb77676ce692ceba9
Quelldatensatz
uspto-grants-2010_10
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07807674B2

Notizen zur Reaktion

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