1-Fluoro-3-iodobenzene → 5-(3-Fluorophenylethynyl)-nicotinic acid ethyl ester

HRID 606928

Reaction equation

HRID 606928 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.I[C:20]1[CH:21]=[C:22]([F:26])[CH:23]=[CH:24][CH:25]=1.[CH2:27]([O:29][C:30](=[O:43])[C:31]1[CH:36]=[C:35]([C:37]#[C:38][Si](C)(C)C)[CH:34]=[N:33][CH:32]=1)[CH3:28]>O1CCCC1.C(OCC)(=O)C.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH2:27]([O:29][C:30](=[O:43])[C:31]1[CH:36]=[C:35]([C:37]#[C:38][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=2)[CH:34]=[N:33][CH:32]=1)[CH3:28]

Participants

8

Reactant 3

HCID 707251-Fluoro-3-iodobenzeneHCID 2724141Tetrabutylammonium FluorideHCID 67047749Ethyl 5-((trimethylsilyl)ethynyl)nicotinate

Product 1

HCID 670477625-(3-Fluorophenylethynyl)-nicotinic acid ethyl esterYield 80%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178419050HCID 178419050, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Add a 1 M solution of tetrabutylammonium fluoride (0.88 g, 3.38 mmol) in tetrahydrofuran to a mixture of 3-iodofluorobenzene (0.50 g, 2.25 mmol), 5-trimethylsilanylethynyl-nicotinic acid ethyl ester, (prepared as described in PREPARATION 16), (0.84 g, 3.38 mmol), bis(triphenylphosphine)palladium (II) dichloride (0.03 g, 0.05 mmol) and copper (I) iodide (0.02 g, 0.09 mmol) at −78° C. Warm to room temperature, stir overnight and then dilute with ethyl acetate. Wash with an aqueous saturated solution of ammonium chloride, dry (magnesium sulfate), filter and concentrate. Purify the residue by silica gel chromatography, eluting with 2.5:45:52.5 ethyl acetate:chloroform:hexanes, to give the title compound as a pale yellow solid (0.46 mg, 80%).

Workup

  1. washWash with an aqueous saturated solution of ammonium chloride
  2. dry with materialdry (magnesium sulfate)
  3. filtrationfilter
  4. concentrationconcentrate
  5. customPurify the residue by silica gel chromatography
  6. washeluting with 2.5:45:52.5 ethyl acetate

Sources & evidence

ORD record
ord-1237bf71b2dd440cace619e612230c93
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Linked notes

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