Diazald → 2-Chloro-3-phenylpyridine

HRID 845206Notes

Reaction equation

HRID 845206 reaction equation
[OH-].[K+].CN(N=O)S([C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=1)(=O)=O.[N+](=C)=[N-].[Cl:20][C:21]1[N:29]=[CH:28][CH:27]=[CH:26]C=1C(O)=O>CCOCC.CO.O.C(O)C>[Cl:20][C:21]1[C:14]([C:11]2[CH:10]=[CH:9][CH:8]=[CH:13][CH:12]=2)=[CH:26][CH:27]=[CH:28][N:29]=1

Participants

9

Reactant 4

HCID 6628DiazaldHCID 9550DiazomethaneHCID 14797Potassium HydroxideHCID 762582-Chloronicotinic acid

Product 1

HCID 27628072-Chloro-3-phenylpyridineYield 100%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

A stirred solution of potassium hydroxide (22.6 g, 0.4 mole), ethanol (45.3 mL), and water (36 mL) was treated with N-methyl N-nitroso-p-toluenesulfonamide (22.6 g, 0.1 mole; Aldrich) in ether (204 mL) at 65°. The rate of addition of the solution was regulated by the rate of distillation of the ether diazomethane solution. A diazomethane generation kit containing all polished glass surfaces was used to distill the ethanol diazomethane solution which was received in two collection vessels connected in tandem, the first cooled to 0° and the second to -78°. The combined diazomethane solutions were treated dropwise with the solution of 2-chloronicotinic acid (4.7 g, 0.03 mole) in methanol at -15°. The reaction mixture was maintained at -15° for 4 hr and then slowly allowed to equilibrate to room temperature. The solution was concentrated in vacuo to a yellow solid, partitioned between aqueous sodium carbonate and methylene chloride, and the organic layer was isolated, dried (MgSO4), and concentrated in vacuo to yield 5.2 g (approximately 100%) of methyl 2-chloronicotinate (VI) as a crude oil suitable for reaction with piperazine as given below.

Workup

  1. additionThe rate of addition of the solution
  2. distillationwas regulated by the rate of distillation of the ether diazomethane solution
  3. additionA diazomethane generation kit containing all polished glass surfaces
  4. distillationto distill the ethanol diazomethane solution which
  5. customwas received in two collection vessels
  6. temperaturethe first cooled to 0°
  7. customsecond to -78°
  8. temperatureThe reaction mixture was maintained at -15° for 4 hr
  9. customto equilibrate to room temperature
  10. concentrationThe solution was concentrated in vacuo to a yellow solid
  11. custompartitioned between aqueous sodium carbonate and methylene chloride
  12. customthe organic layer was isolated
  13. dry with materialdried (MgSO4)
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-76fabbc1173a47638b7a9d87ff5c2659
Source dataset
uspto-grants-1988_07
Patent number
US04757073

Reaction notes

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