Ammonia → 5-Fluoro-2-methoxynicotinaldehyde

HRID 1837713Notes

Reaction equation

HRID 1837713 reaction equation
C([Li])CCC.C[O:7][CH:8](OC)[C:9]1[C:10]([O:16][CH3:17])=[N:11][CH:12]=[C:13](Br)[CH:14]=1.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:30])(=O)=O)=CC=1.Cl.N.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.[Cl-].[Na+].O.CC(C)=O>[F:30][C:13]1[CH:14]=[C:9]([CH:8]=[O:7])[C:10]([O:16][CH3:17])=[N:11][CH:12]=1

Participants

10

Reactant 6

HCID 222AmmoniaHCID 313Hydrochloric Acid2×HCID 11430Potassium CarbonateHCID 588007N-FluorobenzenesulfonimideHCID 22678608HCID 22678608, compoundHCID 178418339Butyllithium

Product 1

HCID 226783235-Fluoro-2-methoxynicotinaldehydeYield 26.4%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 8028TetrahydrofuranSolvent3×HCID 57417360Sodium chloride; waterSolvent

Procedure

20 ml of tetrahydrofuran was cooled to −78° C., 2.41 ml of n-butyllithium (2.6 M, hexane solution) was added thereto, and the mixture was stirred. A solution of 1.50 g of 5-bromo-2-methoxy-3-pyridinecarboxaldehyde dimethyl acetal dissolved in 5 ml of tetrahydrofuran was added dropwise thereinto. After 25 minutes, a solution of 2.16 g of N-fluorobenzenesulfonimide dissolved in 20 ml of tetrahydrofuran was added dropwise thereinto over 20 minutes and the mixture was further stirred for 55 minutes. To the reaction mixture were added brine and 20 ml of 2N-hydrochloric acid, followed by stirring at room temperature. After 40 minutes, a diluted ammonia was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, to give a yellow oil. The oil was dissolved in 16 ml of acetone, 4 ml of 5N-hydrochloric acid was added thereto, and the mixture was left for 30 minutes at room temperature. An aqueous potassium carbonate was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the crude product was purified by silica gel column chromatography (n-hexane:ethyl acetate=15:1), to give 234 mg of the title compound as a slight yellow solid.

Workup

  1. additionwas added dropwise
  2. additionwas added dropwise
  3. waitover 20 minutes
  4. stirringthe mixture was further stirred for 55 minutes
  5. stirringby stirring at room temperature
  6. waitAfter 40 minutes
  7. extractionthe mixture was extracted with ethyl acetate
  8. washThe organic layer was washed with water and brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe solvent was evaporated
  11. customto give a yellow oil
  12. waitthe mixture was left for 30 minutes at room temperature
  13. extractionthe mixture was extracted with ethyl acetate
  14. washThe organic layer was washed with water and brine
  15. dry with materialdried over anhydrous magnesium sulfate
  16. customThe solvent was evaporated
  17. customthe crude product was purified by silica gel column chromatography (n-hexane:ethyl acetate=15:1)

Sources & evidence

ORD record
ord-0af3a69510b44f97b6a94cba703765e8
Source dataset
uspto-grants-2004_08
Patent number
US06784192B2

Reaction notes

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