Pentafluoropyridine → Imidazole

HRID 379612

Reaktionsgleichung

Reaktionsgleichung von HRID 379612
[Li]CCCC.C(OC([N:13]1[C:17]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[C:16]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[N:15]=[CH:14]1)OCC)C.C(OC([N:38]1[C:42](C2C=CC(F)=CC=2)=[C:41](C2C=CN=CC=2)[N:40]=[CH:39]1)OCC)C.[F:56][C:57]1[N:62]=[C:61]([F:63])[C:60]([F:64])=[C:59](F)[C:58]=1[F:66]>C1COCC1>[F:30][C:27]1[CH:26]=[CH:25][C:24]([C:16]2[N:15]=[C:14]([C:59]3[C:58]([F:66])=[C:57]([F:56])[N:62]=[C:61]([F:63])[C:60]=3[F:64])[NH:13][C:17]=2[C:18]2[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=2)=[CH:29][CH:28]=1.[NH:38]1[CH:42]=[CH:41][N:40]=[CH:39]1

Komponenten

7

Edukt 4

HCID 69690PentafluoropyridineHCID 183675041-(1,1-Diethoxymethyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)imidazoleHCID 183675051-(1,1-Diethoxymethyl)-5-(4-fluorophenyl)-4-(4-pyridinyl)imidazoleHCID 178418339Butyllithium

Produkt 2

HCID 795ImidazoleHCID 206927112,3,5,6-Tetrafluoro-4-[4-(4-fluoro-phenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]-pyridine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-55 °C

Versuchsvorschrift

1.6 M nBuLi (66 ml; 45 mmol) is added at −45° C. to a ˜1:1 mixture of 1-(1,1-diethoxymethyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)imidazole and 1-(1,1-diethoxymethyl)-5-(4-fluorophenyl)-4-(4-pyridinyl)imidazole (15 g; 43 mmol) in THF (210 ml). After 15 min. at −45° C. the reaction mixture is cooled to −55° C. and pentafluoropyridine (5.1 ml; 47 mmol) is rapidly introduced. The cooling bath is removed, the reaction mixture allowed to warm to −15° C. and poured on water (1 l), which is then acidified with 2N HCl (100 ml). After stirring for 5 min. the mixture is combined with a saturated solution of Na2CO3 and extracted with ethyl acetate three times. The combined organic phases are dried over Na2SO4, filtered and evaporated to dryness rendering the title compound as brownish crystals (16.3 g). Chromatography (SiO2; acetone/hexanes 1:1) yields the title compound together with some unreacted and unprotected imidazole starting material, which could be removed by washing with acetone yielding the title compound (8.7 g; 52.4%).

Aufarbeitung

  1. customThe cooling bath is removed
  2. temperatureto warm to −15° C.
  3. additionpoured on water (1 l), which
  4. extractionextracted with ethyl acetate three times
  5. dry with materialThe combined organic phases are dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness rendering the title compound as brownish crystals (16.3 g)

Quellen und Nachweise

ORD-Eintrag
ord-b44df5b3ba744d918c9a74fa57fc2599
Quelldatensatz
uspto-grants-2001_10
Patentnummer
US06300347B1

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