Tris(4-fluorophenyl)phosphine → 5-Fluoro-1H-pyrrolo[2,3-b]pyridine

HRID 2382125Notes

Reaction equation

HRID 2382125 reaction equation
[C:1]([C:3]1[C:4]([NH2:10])=[N:5][CH:6]=[C:7]([F:9])[CH:8]=1)#[CH:2].FC1C=CC(P(C2C=CC(F)=CC=2)C2C=CC(F)=CC=2)=CC=1>CN(C=O)C.[Cl-].[Na+].O>[F:9][C:7]1[CH:8]=[C:3]2[CH:1]=[CH:2][NH:10][C:4]2=[N:5][CH:6]=1

Participants

5

Reactant 2

HCID 140387Tris(4-fluorophenyl)phosphineHCID 552886203-Ethynyl-5-fluoropyridin-2-amine

Product 1

HCID 207844625-Fluoro-1H-pyrrolo[2,3-b]pyridineYield 84%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
85 °C

Procedure

A solution of 3-ethynyl-5-fluoro-pyridin-2-ylamine (1.25 g, 9.2 mmol) in DMF (20 mL) is treated with (Rh(cod)2Cl)2 (23 mg, 0.023 mmol) and tris-(4-fluoro-phenyl)-phosphane (115 mg, 0.368 mmol) and stirred at 85° C. for 0.5 h. The mixture is then poured over brine (50 mL), and extracted with EtOAc (3×50 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 35%-75% EtOAc in heptane to afford 5-fluoro-1H-pyrrolo[2,3-b]pyridine (1.05 g, 84%). MS: 137 (M+H); 1H NMR (300 MHz, CDCl3): δ 9.15 (s, NH, 1H), 7.99 (s, 1H), 7.44 (d, 1H), 7.18 (s, 1H), 6.28 (s, 1H).

Workup

  1. extractionextracted with EtOAc (3×50 mL)
  2. dry with materialThe combined organic layer is dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by silica gel chromatography
  6. washeluting with 35%-75% EtOAc in heptane

Sources & evidence

ORD record
ord-921d1eee2f204cf8b60c9476ab9102a4
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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