Ethyl bromodifluoroacetate → Ethyl 2-(5-(4-cyanophenoxy)pyridin-2-yl)-2,2-difluoroacetate

HRID 63253

Reaktionsgleichung

Reaktionsgleichung von HRID 63253
Br[C:2]([F:9])([F:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4].Br[C:11]1[N:16]=[CH:15][C:14]([O:17][C:18]2[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=2)=[CH:13][CH:12]=1>CS(C)=O.C(OCC)(=O)C.[Cu]>[C:22]([C:21]1[CH:20]=[CH:19][C:18]([O:17][C:14]2[CH:13]=[CH:12][C:11]([C:2]([F:9])([F:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4])=[N:16][CH:15]=2)=[CH:25][CH:24]=1)#[N:23]

Komponenten

6

Edukt 2

HCID 69585Ethyl bromodifluoroacetateHCID 451422674-((6-Bromopyridin-3-yl)oxy)benzonitrile

Produkt 1

HCID 90052223Ethyl 2-(5-(4-cyanophenoxy)pyridin-2-yl)-2,2-difluoroacetateAusbeute 56,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23978CopperKatalysatorHCID 679Dimethyl SulfoxideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of ethyl 2-bromo-2,2-difluoroacetate (22.13 mL, 109.05 mmol) and copper (13.85 g, 218.1 mmol) in dry dimethylsulfoxide (DMSO) (80 mL) was stirred at room temperature (rt) for 4 h. 4-((6-Bromopyridin-3-yl)oxy)benzonitrile (10 g, 36.35 mmol) was added and the mixture heated at 50° C. for 16 h. The reaction mixture was cooled to room temperature, diluted with 200 mL of ethyl acetate (EtOAc) and stirred for 10 min. The mixture was filtered through a plug of Celite® and the filtrate was washed with saturated NH4Cl solution to remove any remaining copper. The solution was dried (Na2SO4) and solvent was removed under reduced pressure to give the title compound as brown oil (6.5 g, 56.5%): IR (thin film) 2229, 1767 cm−1; 1H NMR (300 MHz, CDCl3) δ 8.44 (d, J=2.7 Hz, 1H), 7.78 (d, J=8.7 Hz, 1H), 7.73-7.64 (m, 2H), 7.49 (dd, J=8.6, 2.7 Hz, 1H), 7.16-7.07 (m, 2H), 4.39 (q, J=7.1 Hz, 2H), 1.35 (t, J=7.2 Hz, 3H); ESIMS m/z 319 ([M+H]+).

Aufarbeitung

  1. temperaturethe mixture heated at 50° C. for 16 h
  2. temperatureThe reaction mixture was cooled to room temperature
  3. stirringstirred for 10 min
  4. filtrationThe mixture was filtered through a plug of Celite®
  5. washthe filtrate was washed with saturated NH4Cl solution
  6. customto remove any remaining copper
  7. dry with materialThe solution was dried (Na2SO4) and solvent
  8. customwas removed under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-02423e094bc241c49175ffd10b6637c0
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09447073B2

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