1-Ethynyl-4-fluorobenzene → 2-(Benzyloxy)-4-((4-fluorophenyl)ethynyl)-5-(methoxymethoxy)pyridine

HRID 219379Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 219379
[CH2:1]([O:8][C:9]1[CH:14]=[C:13](I)[C:12]([O:16][CH2:17][O:18][CH3:19])=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:20]([C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1)#[CH:21]>O1CCOCC1.[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>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([C:21]#[C:20][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[C:12]([O:16][CH2:17][O:18][CH3:19])=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

6

Edukt 2

HCID 5226271-Ethynyl-4-fluorobenzeneHCID 672174582-(Benzyloxy)-4-iodo-5-(methoxymethoxy)pyridine

Produkt 1

HCID 672176052-(Benzyloxy)-4-((4-fluorophenyl)ethynyl)-5-(methoxymethoxy)pyridineAusbeute 86 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

2-(benzyloxy)-4-iodo-5-(methoxymethoxy)pyridine (3.0 g, 8.08 mmol), copper (I) iodide (92 mg, 0.485 mmol), PdCl2(PPh3)2 (284 mg, 0.404 mmol), 1-ethynyl-4-fluorobenzene (1.07 g, 8.89 mmol) were combined in dioxane (40 mL) and TEA (40 mL), degassed and stirred at 80° C. for 1.5 hrs. The mixture was diluted with EtOAc and washed with sat NaCl and H2O. The organic phase was 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 2-(benzyloxy)-4-((4-fluorophenyl)ethynyl)-5-(methoxymethoxy)pyridine (2.52 g, 6.93 mmol, 86% yield) consistent by LCMS. LC-MS retention time: 2.71 min; m/z (MH+): 364. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters SunFire 5u 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. customTEA (40 mL), degassed
  2. additionThe mixture was diluted with EtOAc
  3. washwashed
  4. dry with materialThe organic phase was dried 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-ed38257ea29242158ed835f5dc453d17
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08198449B2

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