Tetrahydrofuran → 5-(3-Fluorophenylethynyl)-nicotinic acid ethyl ester

HRID 606799

Reaction equation

HRID 606799 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1.I[C:25]1[CH:26]=[C:27]([F:31])[CH:28]=[CH:29][CH:30]=1.[CH2:32]([O:34][C:35](=[O:48])[C:36]1[CH:41]=[C:40]([C:42]#[C:43][Si](C)(C)C)[CH:39]=[N:38][CH:37]=1)[CH3:33].[Cl-].[NH4+]>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>[CH2:32]([O:34][C:35](=[O:48])[C:36]1[CH:41]=[C:40]([C:42]#[C:43][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[CH:26]=2)[CH:39]=[N:38][CH:37]=1)[CH3:33]

Participants

9

Reactant 5

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 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 3

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

Procedure

Add a 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran (0.88 g, 3.38 mmol) to a mixture of 3-iodofluorobenzene (0.50 g, 2.25 mmol), 5-trimethylsilanylethynyl-nicotinic acid ethyl ester (0.84 g, 3.38 mmol), (prepared essentially as described in PREPARATION 16), bis(triphenylphosphine)palladium (II) dichloride (0.03 g, 0.05 mmol) and copper (I) iodide (0.02 g, 0.09 mmol) at −780C. Warm to room temperature, stir overnight and dilute the mixture with ethyl acetate and an aqueous saturated solution of ammonium chloride. Separate the organic layer; dry (magnesium sulfate), filter and concentrate. Purify the resulting 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 g, 80%).

Workup

  1. custom(prepared essentially
  2. customSeparate the organic layer
  3. dry with materialdry (magnesium sulfate)
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify the resulting residue by silica gel chromatography
  7. washeluting with 2.5:45:52.5 ethyl acetate

Sources & evidence

ORD record
ord-a0fe3f254a904a1c9d2c2616b051a16f
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Linked notes

Loading…