2-(Trifluoromethyl)phenylacetonitrile → [5-Chloro-6-oxo-1-(tetrahydro-pyran-2-yl)-1,6-dihydro-pyridazin-4-yl]-(2-trifluoromethyl-phenyl)-acetonitrile

HRID 2381360

Reaktionsgleichung

Reaktionsgleichung von HRID 2381360
[Cl:1][C:2]1[C:3](=[O:15])[N:4]([CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[N:5]=[CH:6][C:7]=1Cl.[F:16][C:17]([F:28])([F:27])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH2:24][C:25]#[N:26].CC(C)([O-])C.[K+]>O1CCCC1>[Cl:1][C:2]1[C:3](=[O:15])[N:4]([CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[N:5]=[CH:6][C:7]=1[CH:24]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:17]([F:16])([F:27])[F:28])[C:25]#[N:26]

Komponenten

5

Edukt 3

HCID 764352-(Trifluoromethyl)phenylacetonitrileHCID 107292624,5-Dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one2×HCID 23665647Potassium tert-butoxide

Produkt 1

HCID 68990773[5-Chloro-6-oxo-1-(tetrahydro-pyran-2-yl)-1,6-dihydro-pyridazin-4-yl]-(2-trifluoromethyl-phenyl)-acetonitrileAusbeute 45,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A solution of 4,5-dichloro-2-(tetrahydropyran-2-yl)-2H-pyridazin-3-one (Intermediate 20, 1.0 g, 4.01 mmol) in tetrahydrofuran (16.7 mL, 0.24M) was treated with (2-trifluoromethyl-phenyl)-acetonitrile (743 mg, 4.01 mmol) followed by potassium tert-butoxide (676 mg, 6.02 mmol). The reaction was heated at 80° C. for 2 h. After this time, the reaction was cooled to 25° C. where it stirred overnight. The reaction mixture was then partitioned between water (100 mL) and methylene chloride (3×75 mL). The combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 40 g, 20-40% ethyl acetate/hexanes) afforded [5-chloro-6-oxo-1-(tetrahydro-pyran-2-yl)-1,6-dihydro-pyridazin-4-yl]-(2-trifluoromethyl-phenyl)-acetonitrile (0.73 g, 45%) as a yellow solid; ES+-HRMS m/e calcd for C18H15N3O2F3Cl [M+H+] 398.0878, found 398.0878.

Aufarbeitung

  1. temperatureAfter this time, the reaction was cooled to 25° C. where it
  2. customThe reaction mixture was then partitioned between water (100 mL) and methylene chloride (3×75 mL)
  3. dry with materialThe combined organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-7da4bc6043684850bd896188636d007b
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08258134B2

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