Diethyl Ether → 5-Acetyloxy-2-chloropyridine

HRID 1437256Notes

Reaction equation

HRID 1437256 reaction equation
F[B-](F)(F)F.[H+].N[C:8]1[CH:9]=[CH:10][C:11]([Cl:14])=[N:12][CH:13]=1.N([O:17][C:18]([CH3:21])(C)C)=O.C([O:24]CC)C>C(O)C>[C:18]([O:17][C:8]1[CH:9]=[CH:10][C:11]([Cl:14])=[N:12][CH:13]=1)(=[O:24])[CH3:21]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 10906Tert-Butyl nitriteHCID 28118Tetrafluoroboric acidHCID 793055-Amino-2-chloropyridine

Product 1

HCID 8199305-Acetyloxy-2-chloropyridine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
-5 °C

Procedure

48% Aqueous tetrafluoroboric acid (40.5 mL) was added to the above-obtained 5-amino-2-chloropyridine (18 g) in ethanol (360 mL), and under cooling at −5° C., tert-butyl nitrite (23.5 mL) was added dropwise to the resultant mixture, followed by stirring for 20 minutes. Diethyl ether was added to the reaction mixture, and the precipitated product was recovered by filtration, followed by drying, to thereby give 6-chloropyridine-3-diazonium tetrafluoroborate (32 g, quantitative amount). The thus-obtained diazonium salt (32 g) in acetic anhydride (160 mL) was heated gradually to 90° C., and the mixture was stirred for 45 minutes, and then cooled in air. The reaction solvent was removed under reduced pressure, and the residue was partitioned between ethyl acetate and water. The organic layer was sequentially washed with water and saturated brine, and then dried over magnesium sulfate anhydrate, followed by filtration. The solvent was removed under reduced pressure, and the residue was purified through silica gel chromatography (hexane-ethyl acetate), to thereby give 5-acetoxy-2-chloropyridine as a solid (10 g, 42%).

Workup

  1. filtrationthe precipitated product was recovered by filtration
  2. customby drying
  3. temperatureThe thus-obtained diazonium salt (32 g) in acetic anhydride (160 mL) was heated gradually to 90° C.
  4. stirringthe mixture was stirred for 45 minutes
  5. temperaturecooled in air
  6. customThe reaction solvent was removed under reduced pressure
  7. customthe residue was partitioned between ethyl acetate and water
  8. washThe organic layer was sequentially washed with water and saturated brine
  9. dry with materialdried over magnesium sulfate anhydrate
  10. filtrationfollowed by filtration
  11. customThe solvent was removed under reduced pressure
  12. customthe residue was purified through silica gel chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-6f757273ec1c44fd9fc6847b803bd636
Source dataset
uspto-grants-2009_11
Patent number
US07622471B2

Reaction notes

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