2-Methyl-2-butene → 1-(4-Fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carboxylic acid

HRID 1050859Notes

Reaction equation

HRID 1050859 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+]>C1COCC1.[OH-].[Na+].CCOC(C)=O.O.C(O)(C)(C)C>[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

10

Reactant 4

HCID 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 5

HCID 962WaterSolventHCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

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) were stirred vigorously in a mixture of THF (35 mL), tert-butanol (35 mL), and water (35 mL) at 0° C. 2-Methyl-2-butene (2.0 M in THF 36.1 mL, 72.2 mmol) was added to the reaction mixture, followed by sodium chlorite (4.8 g, 53.7 mmol). The ice bath was removed and the reaction mixture was warmed to RT and stirred vigorously for 1 h. 1N HCl (20 mL) was added. The mixture was stirred for 5 min. The solids were collected by filtration and washed with water, EtOAc, and ether. The layers of the filtrate were separated, the aqueous layer was extracted with EtOAc, and the combined organics were dried over MgSO4 and concentrated in vacuo. The resulting solid was suspended in EtOAc, filtered, and washed with EtOAc and ether to yield additional product. The pale yellow solids (8.22 g) were combined, dissolved in a minimal amount of 1N aqueous NaOH, treated with EtOAc, and stirred vigourously for 5 min. The layers were separated, and the aqueous layer was washed with EtOAc. The aqueous layer was acidified to pH 1 with conc HCl. The pale yellow solid that precipitated out of solution was collected by filtration, washed with water, EtOAc, and ether, and dried under vacuum to afford 1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carboxylic acid (5.4 g, 64.5% yield). 1H NMR (400 MHz, DMSO-d6): δ 13.5 (s, 1 H), 7.43-7.47 (m, 3 H), 7.30-7.35 (m, 2 H), 6.76 (d, J=7.2 Hz, 1 H).

Workup

  1. customThe ice bath was removed
  2. addition1N HCl (20 mL) was added
  3. stirringThe mixture was stirred for 5 min
  4. filtrationThe solids were collected by filtration
  5. washwashed with water, EtOAc, and ether
  6. customThe layers of the filtrate were separated
  7. extractionthe aqueous layer was extracted with EtOAc
  8. dry with materialthe combined organics were dried over MgSO4
  9. concentrationconcentrated in vacuo
  10. filtrationfiltered
  11. washwashed with EtOAc and ether
  12. customto yield additional product
  13. stirringstirred vigourously for 5 min
  14. customThe layers were separated
  15. washthe aqueous layer was washed with EtOAc
  16. customThe pale yellow solid that precipitated out of solution
  17. filtrationwas collected by filtration
  18. washwashed with water, EtOAc, and ether
  19. customdried under vacuum

Sources & evidence

ORD record
ord-ffce865ea2f94281a3f68ffd0edb3b85
Source dataset
uspto-grants-2016_07
Patent number
US09387202B2

Reaction notes

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