Triethylamine → 5-fluoro-3-methyl-1H-pyrrolo[3,2-b]pyridine

HRID 2382137Notes

Reaction equation

HRID 2382137 reaction equation
[CH2:1]([N:4]([C:11]1[C:12](Br)=[N:13][C:14]([F:17])=[CH:15][CH:16]=1)C(=O)C(F)(F)F)[CH:2]=[CH2:3].[Cl-].C([NH3+])CCC.C([NH3+])CCC.C([NH3+])CCC.C([NH3+])CCC.[Cl-].[Cl-].[Cl-].C(N(CC)CC)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:17][C:14]1[N:13]=[C:12]2[C:2]([CH3:3])=[CH:1][NH:4][C:11]2=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 86639385N-allyl-N-(2-bromo-6-fluoro-pyridin-3-yl)-2,2,2-trifluoro-acetamideHCID 86639386Tetra(n-butylammonium) chloride

Product 1

HCID 685551555-fluoro-3-methyl-1H-pyrrolo[3,2-b]pyridineYield 95.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of N-allyl-N-(2-bromo-6-fluoro-pyridin-3-yl)-2,2,2-trifluoro-acetamide (3.41 g, 10.43 mmol), palladium acetate (94 mg, 0.42 mmol), tetra(n-butylammonium) chloride (3.19 g, 11.47 mmol) and triethylamine (2.37 g, 23.4 mmol) in anhydrous DMF (20 mL) is stirred at 10° C. under N2 for an hour. DMF is evaporated off and the residue is mixed with water (12 mL) and stirred at rt for an hour. EtOAc (15 mL) is added and stirred at rt overnight. The organic layer is separated and the aqueous layer is extracted with EtOAc (35 mL). The combined organic layer is dried (Na2SO4), filtered, and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 10-60% EtOAc in heptane to afford 5-fluoro-3-methyl-1H-pyrrolo[3,2-b]pyridine (1.5 g) as a solid. MS: 151 (M+H); 1H NMR (300 MHz, CDCl3) δ 2.38(s, 3H), 6.77(d, H), 7.28(s, H), 7.74(dd, H).

Workup

  1. customDMF is evaporated off
  2. additionthe residue is mixed with water (12 mL)
  3. additionEtOAc (15 mL) is added
  4. stirringstirred at rt overnight
  5. customThe organic layer is separated
  6. extractionthe aqueous layer is extracted with EtOAc (35 mL)
  7. dry with materialThe combined organic layer is dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue is purified by silica gel chromatography
  11. washeluting with 10-60% EtOAc in heptane

Sources & evidence

ORD record
ord-a28f914a70704e418dd39998762c6f20
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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