Ethyl Acetate → 4-(2-Fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid

HRID 917776Notes

Reaction equation

HRID 917776 reaction equation
Cl[C:2]1[C:3]([C:10]([OH:12])=[O:11])=[CH:4][N:5]([CH3:9])[C:6](=[O:8])[CH:7]=1.[F:13][C:14]1[CH:20]=[C:19]([I:21])[CH:18]=[CH:17][C:15]=1[NH2:16].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C(OCC)(=O)C>Cl.O>[F:13][C:14]1[CH:20]=[C:19]([I:21])[CH:18]=[CH:17][C:15]=1[NH:16][C:2]1[C:3]([C:10]([OH:12])=[O:11])=[CH:4][N:5]([CH3:9])[C:6](=[O:8])[CH:7]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 1856942-Fluoro-4-iodoanilineHCID 2733832Lithium HexamethyldisilazideHCID 116655334-Chloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid

Product 1

HCID 112346084-(2-Fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylic acidYield 41.4%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent

Procedure

4-Chloro-1-methyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid (133 mg, 0.709 mmol) and 2-fluoro-4-iodoaniline (172 mg, 0.726 mmol) were combined in a round bottom flask equipped with magenetic stir bar. The flask was immersed in an ice bath and lithium bis(trimethylsilyl)amide (1.0 M in tetrahydrofuran, 5.0 mL, 5.0 mmol) was added slowly (5 min) with vigorous stirring under an atmosphere of nitrogen. The reaction mixture was further stirred for 1 h at 0° C. and 1 h at ambient temperature. The reaction mixture was diluted with 1 M hydrochloric acid and water and was extracted with ethyl acetate (3×). The extracts were dried over magnesium sulfate and concentrated in vacuo. Upon concentrateion, 4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid (114 mg, 41% yield) was isolated directly from the ethyl acetate by filtration and drying in vacuo: 1H NMR (DMSO-d6, 400 MHz) δ 13.30 (v br s, 1H), 9.66 (s, 1H), 8.52 (s, 1H), 7.76 (dd, J=10.1, 1.9 Hz, 1H), 7.59 (br d, J=8.5 Hz, 1H), 7.31 (t, J=8.5 Hz, 1H), 5.49 (s, 1H), 3.41 (s, 3H); MS (APCI+) 388.9.

Workup

  1. customequipped with magenetic stir bar
  2. customThe flask was immersed in an ice bath
  3. stirringThe reaction mixture was further stirred for 1 h at 0° C. and 1 h at ambient temperature
  4. extractionwas extracted with ethyl acetate (3×)
  5. dry with materialThe extracts were dried over magnesium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-772acc078e114e86a96e2e8b29574daa
Source dataset
uspto-grants-2007_09
Patent number
US07273877B2

Reaction notes

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