Formamide → 5-[(4-Chlorophenyl)methoxy]pyridine-2-carboxamide

HRID 1995825Notes

Reaction equation

HRID 1995825 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][O:7][C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)=[CH:4][CH:3]=1.S(=O)(=O)(O)O.OO.C(OCC)(=O)C.[CH:29]([NH2:31])=[O:30]>C(Cl)(Cl)Cl.O>[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][C:11]([C:29]([NH2:31])=[O:30])=[N:10][CH:9]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 713FormamideHCID 784Hydrogen PeroxideHCID 1118Sulfuric AcidHCID 8857Ethyl AcetateHCID 198310963-[(4-Chlorophenyl)methoxy]pyridine

Product 1

HCID 204861105-[(4-Chlorophenyl)methoxy]pyridine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

To 3-(4-chlorobenzyloxy)pyridine (2.19 g, 10 mmol) in formamide (10 ml) at 10° is slowly added conc. sulfuric acid. The reaction is then cooled to 5°, and FeSO4.7H2O (4.16 g, 15 mmol), finely powdered, and hydrogen peroxide (1.7 ml of 30% solution, 0.51 g of H2O2, 15 mmol) are added simultaneously over 10 minutes, with rapid stirring and cooling to 12°-18°. After addition is complete, the reaction is allowed to sit at RT overnight. Ethyl acetate and water are added to the reaction slurry. The layers are separated, and the aqueous phase is extracted with ethyl acetate (3×). The combined organic layers are washed with water and with brine and are dried over calcium sulfate. The residue is taken up in ether, leaving an oily residue. The oily residue is then taken up in chloroform, washed with sat. sodium carbonate, with water and with brine and purified by preparative thin layer chromatography (developing with 50% ethyl acetate/hexane and 0.05% ammonium hydroxide). The second band is collected, yielding 5-(4-chlorobenzyloxy)pyridine-2-carboxamide.

Workup

  1. customat 10°
  2. temperatureThe reaction is then cooled to 5°
  3. temperaturecooling to 12°-18°
  4. additionAfter addition
  5. customThe layers are separated
  6. extractionthe aqueous phase is extracted with ethyl acetate (3×)
  7. washThe combined organic layers are washed with water and with brine
  8. dry with materialare dried over calcium sulfate
  9. customleaving an oily residue
  10. washwashed with sat. sodium carbonate, with water and with brine
  11. custompurified by preparative thin layer chromatography (developing with 50% ethyl acetate/hexane and 0.05% ammonium hydroxide)
  12. customThe second band is collected

Sources & evidence

ORD record
ord-e12ae815b30a4ca5842c8d2de9ad4106
Source dataset
uspto-grants-1983_09
Patent number
US04406690

Reaction notes

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