Hydrochloric Acid → 1-(4-Fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carboxylic acid

HRID 1472608Notes

Reaction equation

HRID 1472608 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][C:11]([I:14])=[C:10]([CH:15]=[O:16])[C:9]2=[O:17])=[CH:4][CH:3]=1.[OH:18]P([O-])(O)=O.[Na+].CC(=CC)C.Cl([O-])=O.[Na+].Cl>C1COCC1.CC(O)(C)C.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH:13]=[CH:12][C:11]([I:14])=[C:10]([C:15]([OH:18])=[O:16])[C:9]2=[O:17])=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 252319761-(4-Fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde

Product 1

HCID 595946501-(4-Fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carboxylic acidYield 65.4%

Reagents, catalysts & solvents 1

HCID 22124471t-Butanol tetrahydrofuran waterSolvent

Procedure

A 0° C. mixture of 1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde (8 g, 23 mmol) and sodium phosphate monobasic (8 g, 58.4 mmol) in 1:1:1 THF/t-BuOH/water (105 mL) was treated with 2-methyl-2-butene (2.0 M in THF, 36.1 mL, 72.2 mmol) followed by sodium chlorite (4.8 g, 53.7 mmol) and the vigorously stirred mixture warmed to RT and stirred for 1 h. HCl (1 M, 20 mL) was added, the mixture stirred for 5 minutes and the solid was collected via filtration and washed with water, EtOAc, then Et2O. The layers of the filtrate were separated and the aqueous layer extracted with additional EtOAc. The combined organics were dried over MgSO4, concentrated to dryness, the residue suspended in EtOAc, the solid collected via filtration and combined with the above-isolated solid. The combined material was dissolved in a minimum amount of 1N NaOH, treated with EtOAc, stirred vigorously for 5 minutes and the layers separated. The aqueous layer was washed with EtOAc, acidified to pH=1 with conc. HCl and the resulting solid was collected via filtration, washed with water, EtOAc and Et2O and dried to afford 1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carboxylic acid (5.4 g, 65%). 1H NMR (400 MHz, DMSO-d6): δ 13.5 (brs, 1H), 7.43-7.47 (m, 3H), 7.30-7.35 (m, 2H), 6.76 (d, J=7.2 Hz, 1H).

Workup

  1. stirringthe mixture stirred for 5 minutes
  2. filtrationthe solid was collected via filtration
  3. washwashed with water, EtOAc
  4. customThe layers of the filtrate were separated
  5. extractionthe aqueous layer extracted with additional EtOAc
  6. dry with materialThe combined organics were dried over MgSO4
  7. concentrationconcentrated to dryness
  8. filtrationthe solid collected via filtration
  9. dissolutionThe combined material was dissolved in a minimum amount of 1N NaOH
  10. additiontreated with EtOAc
  11. stirringstirred vigorously for 5 minutes
  12. customthe layers separated
  13. washThe aqueous layer was washed with EtOAc
  14. filtrationthe resulting solid was collected via filtration
  15. washwashed with water, EtOAc and Et2O
  16. customdried

Sources & evidence

ORD record
ord-1ebe3673d43a41e6bea756075048d1f8
Source dataset
uspto-grants-2015_04
Patent number
US09012635B2

Reaction notes

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