1-Bromo-2,4-difluorobenzene → 4-((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-oxoethyl)pyridin-3-yl)oxy)benzonitrile

HRID 63254

Reaktionsgleichung

Reaktionsgleichung von HRID 63254
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[F:9].[Li]CCCC.[C:15]([C:17]1[CH:37]=[CH:36][C:20]([O:21][C:22]2[CH:23]=[CH:24][C:25]([C:28]([F:35])([F:34])[C:29](OCC)=[O:30])=[N:26][CH:27]=2)=[CH:19][CH:18]=1)#[N:16]>C(OCC)C>[F:9][C:3]1[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=1[C:29](=[O:30])[C:28]([C:25]1[N:26]=[CH:27][C:22]([O:21][C:20]2[CH:19]=[CH:18][C:17]([C:15]#[N:16])=[CH:37][CH:36]=2)=[CH:23][CH:24]=1)([F:34])[F:35]

Komponenten

5

Edukt 3

HCID 676741-Bromo-2,4-difluorobenzeneHCID 90052223Ethyl 2-(5-(4-cyanophenoxy)pyridin-2-yl)-2,2-difluoroacetateHCID 178418339Butyllithium

Produkt 1

HCID 900521254-((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2-oxoethyl)pyridin-3-yl)oxy)benzonitrile

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3283Diethyl EtherLösungsmittel2×

Versuchsvorschrift

To a solution of 1-bromo-2,4-difluorobenzene (0.724 g, 3.77 mmol) in diethyl ether (Et2O)(20 mL) under a N2 atmosphere was added n-BuLi (2.49 mL, 4.03 mmol) at −78° C. and the reaction mixture was stirred for 45 minutes. Ethyl 2-(5-(4-cyanophenoxy)pyridin-2-yl)-2,2-difluoroacetate (1.00 g, 3.1 mmol) in Et2O (5 mL) was added dropwise and the reaction was stirred at the same temperature for 1 h. The reaction mixture was carefully quenched with 1N HCl until the reaction mixture was acidic. The reaction mixture was allowed to warm to room temperature and was extracted with Et2O. The combined organic phases were dried (Na2SO4) and concentrated to afford the title compound as yellow solid that was used for the next step without further purification (1.0 g, 83% crude yield): 1H NMR (300 MHz, CDCl3) δ 8.36 (d, J=2.7 Hz, 1H), 8.15-8.02 (m, 1H), 7.86 (d, J=8.7 Hz, 1H), 7.74-7.65 (m, 2H), 7.53 (dd, J=8.6, 2.7 Hz, 1H), 7.16-7.06 (m, 2H), 7.05-6.96 (m, 1H), 6.84 (ddd, J=10.9, 8.6, 2.4 Hz, 1H); 19F NMR (376 MHz, CDCl3) δ −99.13 (d, J=13.5 Hz), −100.67 (d, J=14.9 Hz), −101.82 (dd, J=28.5, 14.2 Hz); ESIMS m/z 387 ([M+1]+).

Aufarbeitung

  1. stirringthe reaction was stirred at the same temperature for 1 h
  2. customThe reaction mixture was carefully quenched with 1N HCl until the reaction mixture
  3. extractionwas extracted with Et2O
  4. dry with materialThe combined organic phases were dried (Na2SO4)
  5. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-41456b0e4da845108fff41fe16983756
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09447073B2

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