Potassium tert-butoxide → 5-Trifluoromethyl-1H-Pyrrolo[2,3-B]Pyridine

HRID 887332Notes

Reaction equation

HRID 887332 reaction equation
CC(C)([O-])C.[K+].[F:7][C:8]([F:23])([F:22])[C:9]1[CH:10]=[C:11]([C:16]#[C:17][Si](C)(C)C)[C:12]([NH2:15])=[N:13][CH:14]=1>CN1C(=O)CCC1.[Cl-].[Na+].O.C(OCC)(=O)C>[F:7][C:8]([F:23])([F:22])[C:9]1[CH:10]=[C:11]2[CH:16]=[CH:17][NH:15][C:12]2=[N:13][CH:14]=1

Participants

6

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 467368715-(Trifluoromethyl)-3-((trimethylsilyl)ethynyl)-pyridin-2-amine

Product 1

HCID 307721175-Trifluoromethyl-1H-Pyrrolo[2,3-B]PyridineYield 59.3%

Reagents, catalysts & solvents 3

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a stirred solution of potassium tert-butoxide (53.6 g, 479 mmol) in anhydrous NMP (200 mL) under a nitrogen atmosphere at 80° C. was added a solution of 5-trifluoromethyl-3-((trimethylsilyl)ethynyl)pyridin-2-amine (62 g, 239 mmol) in NMP (100 mL) at a rate to maintain the internal temperature below 100° C. After complete addition the reaction was deemed complete by LCMS. The reaction mixture was allowed to cool to room temperature and poured carefully into saturated brine (700 mL) cooled in an ice bath to 10° C. The precipitate that formed was aged for 45 min at this temperature and isolated by filtration through buchner funnel. The collected precipitate was stirred in ethyl acetate (1 litre) and water then filtered through celite to remove insoluble polymeric material and organic layer was separated. The aqueous layer was further extracted with ethyl acetate and the combined organic layers dried over magnesium sulfate and concentrated to give a brown solid which was triturated by stirring for an hour in hot heptane and then cooling before filtration, to afford 5-Trifluoromethyl-1H-pyrrolo[2,3-b]pyridine as a crystalline solid (26.38 g, 59% yield).

Workup

  1. temperatureto maintain the internal temperature below 100° C
  2. additionAfter complete addition the reaction
  3. temperaturecooled in an ice bath to 10° C
  4. customThe precipitate that formed
  5. customisolated by filtration through buchner funnel
  6. filtrationwater then filtered through celite
  7. customto remove insoluble polymeric material and organic layer
  8. customwas separated
  9. extractionThe aqueous layer was further extracted with ethyl acetate
  10. dry with materialthe combined organic layers dried over magnesium sulfate
  11. concentrationconcentrated
  12. customto give a brown solid which
  13. customwas triturated
  14. temperaturecooling before filtration

Sources & evidence

ORD record
ord-28703846eaff4f599ecd2bccb85742c7
Source dataset
uspto-grants-2012_08
Patent number
US08247421B2

Reaction notes

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