Iodine → 5-(3-Cyano-4-fluorophenylethynyl)-nicotinonitrile

HRID 606952Notes

Reaction equation

HRID 606952 reaction equation
[OH-].[NH4+:2].II.[F:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]#[C:13][C:14]2[CH:15]=[N:16][CH:17]=[C:18]([CH:21]=2)[C:19]#[N:20])=[CH:8][C:7]=1[CH:22]=O>O1CCCC1>[C:22]([C:7]1[CH:8]=[C:9]([C:12]#[C:13][C:14]2[CH:15]=[N:16][CH:17]=[C:18]([CH:21]=2)[C:19]#[N:20])[CH:10]=[CH:11][C:6]=1[F:5])#[N:2]

Participants

5

Reactant 3

HCID 807IodineHCID 14923Ammonium HydroxideHCID 848197895-((4-Fluoro-3-formylphenyl)ethynyl)nicotinonitrile

Product 1

HCID 670476325-(3-Cyano-4-fluorophenylethynyl)-nicotinonitrileYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add a 28% aqueous solution of ammonium hydroxide (10 mL) and iodine (279 mg, 1.10 mmol) to a solution of 5-(4-fluoro-3-formylphenylethynyl) -nicotinonitrile, (prepared as described in PREPARATION 38), (250 mg, 1.00 mmol) in tetrahydrofuran (5 mL). After 3.25 h quench with a 5% aqueous solution of sodium bisulfite (5 mL) and extract twice with ethyl acetate. Wash the organic layers with saturated aqueous sodium chloride, dry (sodium sulfate), filter, and concentrate. Dissolve the crude solid in dichloromethane and add PS-TsNNH2 (3g, ˜1.2 mmol, Argonaut). Stir the mixture for 20 min and filter through diatomaceous earth. Purify by silica gel chromatography, eluting with 90:10 to 80:20 (70:30 hexanes:dichloromethane):ethyl acetate, to give the title compound as a white crystalline solid (140 mg, 57%).

Workup

  1. customAfter 3.25 h quench with a 5% aqueous solution of sodium bisulfite (5 mL)
  2. extractionextract twice with ethyl acetate
  3. washWash the organic layers with saturated aqueous sodium chloride
  4. dry with materialdry (sodium sulfate)
  5. filtrationfilter
  6. concentrationconcentrate
  7. dissolutionDissolve the crude solid in dichloromethane
  8. additionadd PS-TsNNH2 (3g, ˜1.2 mmol, Argonaut)
  9. filtrationfilter through diatomaceous earth
  10. customPurify by silica gel chromatography
  11. washeluting with 90:10 to 80:20 (70:30 hexanes:dichloromethane)

Sources & evidence

ORD record
ord-07202ce9c4004f88810bc05d6b528441
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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