Water → Methyl 2-(4-fluorophenoxy)-5-iodonicotinate

HRID 1293196Notes

Reaction equation

HRID 1293196 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:12]1[N:21]=[CH:20][C:19]([I:22])=[CH:18][C:13]=1[C:14]([O:16][CH3:17])=[O:15].O>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:12]2[N:21]=[CH:20][C:19]([I:22])=[CH:18][C:13]=2[C:14]([O:16][CH3:17])=[O:15])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 97324-FluorophenolHCID 24758Sodium hydrideHCID 2764559Methyl 2-Chloro-5-iodonicotinate

Product 1

HCID 57572293Methyl 2-(4-fluorophenoxy)-5-iodonicotinateYield 86.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-fluorophenol (224 mg, 2.0 mmol) in DMF (5.0 mL) was added sodium hydride (48 mg, 2.0 mmol) at room temperature. After stirring for 10 min, methyl 2-chloro-5-iodonicotinate (J. Org. Chem. 1989, 54, 3618, 594 mg, 2.0 mmol) was added to the reaction mixture. The reaction mixture was stirred under reflux for 16 h. Then the reaction mixture was poured into water (50 mL) and extracted with ether (50 mL×3). The combined organic extracts were washed with brine (50 mL) and dried (sodium sulfate). After removal of the solvent, the residue was purified by flash column chromatography on silica gel (50 g) eluting with hexane/ethyl acetate (2/1) to afford 644 mg (86%) of the title compound: 1H-NMR (CDCl3) δ 8.51 (1H, d, J=2.3 Hz), 8.41 (1H, s), 7.09 (4H, d, J=6.2 Hz), 3.95 (3H, s); MS (ESI) m/z 374 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred
  2. temperatureunder reflux for 16 h
  3. extractionextracted with ether (50 mL×3)
  4. washThe combined organic extracts were washed with brine (50 mL)
  5. dry with materialdried (sodium sulfate)
  6. customAfter removal of the solvent
  7. customthe residue was purified by flash column chromatography on silica gel (50 g)
  8. washeluting with hexane/ethyl acetate (2/1)

Sources & evidence

ORD record
ord-2390f34784474e11a5c7b973eb8902a8
Source dataset
uspto-grants-2007_07
Patent number
US07238714B2

Reaction notes

Loading…