Potassium Carbonate → HCID 22993884, compound

HRID 1167665Notes

Reaction equation

HRID 1167665 reaction equation
[CH3:1][C:2]([C:4]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[CH:7]=[CH:6][C:5]=1F)=[O:3].[Cl:14][C:15]1[CH:16]=[C:17]([OH:21])[CH:18]=[N:19][CH:20]=1.C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[Cl:14][C:15]1[CH:16]=[C:17]([O:21][CH2:1][C:2]([C:4]2[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[CH:7]=[CH:6][CH:5]=2)=[O:3])[CH:18]=[N:19][CH:20]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 5823053-Hydroxy-5-chloropyridineHCID 27810671-(2-Fluoro-5-nitrophenyl)ethan-1-one

Product 1

HCID 22993884HCID 22993884, compoundYield 68.3%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

2-Fluoro-5-nitroacetophenone (3.6 g, 20 mmol, described by Cooper, et. al. J. Med. Chem. 33:1246-1252 (1990)) and 5-chloro-3-pyridinol (3.2 g, 25 mmol) were dissolved in acetone (20 mL). After addition of solid K2CO3 (3.5 g, 26 mmol), the reaction mixture was heated to reflux for 4 hr. The reaction mixture was cooled and acetone was removed under reduced pressure. The residue was suspended in deionized water (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic portions were washed with saturated brine, dried over MgSO4, filtered, and concentrated to a brown oil which was partially purified by column chromatography (silica gel, 4:1 hexanes:ethyl acetate) to provide 4 g of 2-(5-chloro-3-pyridyloxy)-5-nitro-1-phenylethanone. This material was dissolved in ethanol (40 mL) and acetic acid (5.3 mL, 93 mmol) to which iron powder (300 mesh, 2.6 g, 46.5 mmol) was added. The reaction mixture was heated to reflux for two days. After removal of excess iron (with a magnetic stir-bar retriever), the reaction mixture was poured into 300 mL of deionized water and extracted with ethyl acetate (3×100 mL). The combined organic portions were washed with saturated brine, dried over MgSO4, filtered, and concentrated to a brown oil which was purified by column chromatography (silica gel, 4:1 hexanes:ethyl acetate). The product 5′-amino-2′-(5-chloro-3-pyridyloxy)-1-phenylethanone was obtained as a yellow oil (1.03g).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 4 hr
  3. temperatureThe reaction mixture was cooled
  4. customacetone was removed under reduced pressure
  5. extractionextracted with ethyl acetate (3×50 mL)
  6. washThe combined organic portions were washed with saturated brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to a brown oil which
  10. customwas partially purified by column chromatography (silica gel, 4:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-fc78d01bec7d40b7b7ed309c591590a7
Source dataset
uspto-grants-2003_09
Patent number
US06620827B2

Reaction notes

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