Pentafluoropyridine → Imidazole

HRID 379612

Reaction equation

HRID 379612 reaction equation
[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

Participants

7

Reactant 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

Product 2

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-55 °C

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-b44df5b3ba744d918c9a74fa57fc2599
Source dataset
uspto-grants-2001_10
Patent number
US06300347B1

Linked notes

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