Sodium Cyanide → Methyl 5-cyano-2-(4-fluorophenoxy)nicotinate

HRID 1293201Notes

Reaction equation

HRID 1293201 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([O:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[C-:20]#[N:21].[Na+]>C(#N)CC.[Cu](I)I>[C:20]([C:2]1[CH:3]=[N:4][C:5]([O:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8])#[N:21]

Participants

5

Reactant 2

HCID 8929Sodium CyanideHCID 57572305HCID 57572305, compound

Product 1

HCID 69051385Methyl 5-cyano-2-(4-fluorophenoxy)nicotinateYield 71.3%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 7854PropionitrileSolvent

Procedure

A mixture of methyl 5-bromo-2-(4-fluorophenoxy)nicotinate (step 1, 163 mg, 0.50 mmol), sodium cyanide (49 mg, 1.0 mmol), tetrakis(triphenylphohphine) palladium(0) (29 mg, 0.025 mmol), and copper iodide (9.5 mg, 0.05 mmol) in propionitrile (4.0 mL) was heated under reflux for 4.5 h with stirring. The reaction mixture was filtered through a pad of Celite®. The filtrate was partitioned between water (10 mL) and dichloromethane (30 mL). The organic phase was separated, dried (sodium sulfate), and concentrated. The residue was purified by TLC plate developing with hexane/ethyl acetate (3/1) to afford 97 mg (71%) of the title compound: 1H-NMR (CDCl3) δ 8.5 (2H, m), 7.14 (2H, d, J=1.2 Hz), 7.12 (2H, s), 3.99 (3H, s); MS (ESI) m/z 272 (M+).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 4.5 h
  3. filtrationThe reaction mixture was filtered through a pad of Celite®
  4. customThe filtrate was partitioned between water (10 mL) and dichloromethane (30 mL)
  5. customThe organic phase was separated
  6. dry with materialdried (sodium sulfate)
  7. concentrationconcentrated
  8. customThe residue was purified by TLC plate

Sources & evidence

ORD record
ord-78234e9beb5d4c90a635478c61814a85
Source dataset
uspto-grants-2007_07
Patent number
US07238714B2

Reaction notes

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