Pentafluoropyridine → 2-(4-Fluorophenyl)-3-(pyridin-4-yl)-4-(2,3,5,6-tetrafluoropyridin-4-yl)-1H-pyrrole

HRID 1244990Notes

Reaction equation

HRID 1244990 reaction equation
C([Li])(C)(C)C.Br[C:7]1[C:8]([C:29]2[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=2)=[C:9]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[N:10]([Si](C(C)C)(C(C)C)C(C)C)[CH:11]=1.[F:35][C:36]1[N:41]=[C:40]([F:42])[C:39]([F:43])=[C:38](F)[C:37]=1[F:45]>CCCCC.O1CCCC1>[F:28][C:25]1[CH:24]=[CH:23][C:22]([C:9]2[NH:10][CH:11]=[C:7]([C:38]3[C:37]([F:45])=[C:36]([F:35])[N:41]=[C:40]([F:42])[C:39]=3[F:43])[C:8]=2[C:29]2[CH:30]=[CH:31][N:32]=[CH:33][CH:34]=2)=[CH:27][CH:26]=1

Participants

6

Reactant 3

HCID 69690PentafluoropyridineHCID 219227844-Bromo-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1-triisopropylsilyl-1H-pyrroleHCID 178418306HCID 178418306, compound

Product 1

HCID 101782582-(4-Fluorophenyl)-3-(pyridin-4-yl)-4-(2,3,5,6-tetrafluoropyridin-4-yl)-1H-pyrroleYield 65.2%

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

1.8 ml (2.75 mmol) of 1.54 N solution of t-butyllithium in pentane were added to a solution of 650 mg (1.37 mmol) of 4-bromo-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1-triisopropylsilyl-1H-pyrrole [prepared as described in step 7(iii) above] in 15 ml of tetrahydrofuran at −78° C. and the mixture was stirred for 10 minutes. At the end of this time, 165 μl (1.51 mmol) of pentafluoropyridine were added to the reaction mixture. The cooling bath was then removed and the mixture was stirred for 30 minutes. At the end of this time, 70 ml of water and 50 ml of a saturated aqueous solution of sodium hydrogencarbonate were added to the reaction mixture, and then this was extracted with ethyl acetate. The organic extract was washed with water and then concentrated by evaporation under reduced pressure. The residue thus obtained was purified by chromatography on a silica gel column using a 4:1 by volume mixture of hexane and ethyl acetate as the eluant to give 346 mg (yield 65%) of the title compound as a pale yellow powder.

Workup

  1. customThe cooling bath was then removed
  2. stirringthe mixture was stirred for 30 minutes
  3. additionAt the end of this time, 70 ml of water and 50 ml of a saturated aqueous solution of sodium hydrogencarbonate were added to the reaction mixture
  4. extractionthis was extracted with ethyl acetate
  5. extractionThe organic extract
  6. washwas washed with water
  7. concentrationconcentrated by evaporation under reduced pressure
  8. customThe residue thus obtained
  9. customwas purified by chromatography on a silica gel column
  10. additionby volume mixture of hexane and ethyl acetate as the eluant

Sources & evidence

ORD record
ord-5d7ebdc506e1471789a17fb463dfab0f
Source dataset
uspto-grants-2006_10
Patent number
US07122666B2

Reaction notes

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