3-Fluoro-5-iodopicolinonitrile → Methyl 2-(6-cyano-5-fluoropyridin-3-yl)-6-fluorobenzoate

HRID 1374162Notes

Reaction equation

HRID 1374162 reaction equation
[F:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[C:6](I)[CH:7]=1.[F:11][C:12]1[C:13]([C:20]([O:22][CH3:23])=[O:21])=[C:14]([Zn]I)[CH:15]=[CH:16][CH:17]=1>C1COCC1>[C:9]([C:3]1[N:4]=[CH:5][C:6]([C:14]2[CH:15]=[CH:16][CH:17]=[C:12]([F:11])[C:13]=2[C:20]([O:22][CH3:23])=[O:21])=[CH:7][C:2]=1[F:1])#[N:10]

Participants

4

Reactant 2

HCID 210758683-Fluoro-5-iodopicolinonitrileHCID 178498692HCID 178498692, compound

Product 1

HCID 21075884Methyl 2-(6-cyano-5-fluoropyridin-3-yl)-6-fluorobenzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3-fluoro-5-iodopyridine-2-carbonitrile (1.08 g, 3.87 mmol) in 10 mL of THF and palladium tetrakistriphenylphosphine (0.18 g, 0.16 mmol) was added to a solution of [3-fluoro-2-(methoxycarbonyl)phenyl](iodo)zinc (prepared from methyl 2-fluoro-6-iodobenzoate and Reike Zinc) in 20 mL of THF via cannula. The mixture was heated to reflux for one hour, cooled, and partitioned between ethyl acetate and water. The organic extract was washed with brine, dried over MgSO4, filtered and concentrated under vacuum. The residue was subjected to silica gel chromatography eluted with 0–20% ethyl acetate in hexanes to provide methyl 2-(6-cyano-5-fluoropyridin-3-yl)-6-fluorobenzoate that gave proton NMR spectra consistent with theory.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for one hour
  3. temperaturecooled
  4. custompartitioned between ethyl acetate and water
  5. extractionThe organic extract
  6. washwas washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. washeluted with 0–20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-bc86ad7b1b81453584731b89221b3090
Source dataset
uspto-grants-2007_01
Patent number
US07163951B2

Reaction notes

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