Nitrogen → 6-Bromo-2-((4-fluorophenyl)ethynyl)pyridin-3-yl acetate

HRID 2068372

Reaktionsgleichung

Reaktionsgleichung von HRID 2068372
[C:1]([O:4][C:5]1[C:6](I)=[N:7][C:8]([Br:11])=[CH:9][CH:10]=1)(=[O:3])[CH3:2].[C:13]([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)#[CH:14].N#N>C(N(CC)CC)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([O:4][C:5]1[C:6]([C:14]#[C:13][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=[N:7][C:8]([Br:11])=[CH:9][CH:10]=1)(=[O:3])[CH3:2]

Komponenten

7

Edukt 3

HCID 947NitrogenHCID 5226271-Ethynyl-4-fluorobenzeneHCID 866399576-Bromo-2-iodopyridin-3-yl acetate

Produkt 1

HCID 866399586-Bromo-2-((4-fluorophenyl)ethynyl)pyridin-3-yl acetateAusbeute 73,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

6-bromo-2-iodopyridin-3-yl acetate (3.50 g, 10.24 mmol), 1-ethynyl-4-fluorobenzene (1.11 g, 9.21 mmol), copper (I) iodide (117 mg, 0.614 mmol), trans-dichlorobis(triphenylphosphine)palladium (II) (359 mg, 0.512 mmol) were combined and evacuated/backfilled with N2 (3×) then diluted with triethylamine (100 ml) and heated to 85° C. for 2 hours. The solvent was evaporated and the reaction was dissolved in EtOAc. The organic phase was washed with water (50 mL) and brine, dried over Na2SO4, filtered, and concentrated and was purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm) to give the expected product 6-bromo-2-((4-fluorophenyl)ethynyl)pyridin-3-yl acetate (2.26 g, 6.76 mmol, 66.1% yield) consistent by NMR. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.77 (2H, s), 7.70 (2H, dd, J=8.78, 5.52 Hz), 7.34 (2H, t, J=8.91 Hz), 2.41 (3H, s). LC-MS retention time: 2.18 min; m/z: parent ion not observed, -Ac: 292, 294. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters SunFire 5 u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode.

Aufarbeitung

  1. customThe solvent was evaporated
  2. dissolutionthe reaction was dissolved in EtOAc
  3. washThe organic phase was washed with water (50 mL) and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customwas purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm)

Quellen und Nachweise

ORD-Eintrag
ord-67839e269e5a4bf48e165bcc6292f86e
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08293909B2

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