Hydrochloric Acid → (3-(Tert-butyldimethylsilyloxy)-4-fluorophenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone

HRID 1712778

Reaktionsgleichung

Reaktionsgleichung von HRID 1712778
Br[C:2]1[CH:7]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:5]=[C:4]([F:15])[CH:3]=1.[Li]CCCC.[Si:21]([O:28][C:29]1[CH:30]=[C:31]([CH:38]=[CH:39][C:40]=1[F:41])[C:32](N(OC)C)=[O:33])([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22].Cl>CCOCC>[Si:21]([O:28][C:29]1[CH:30]=[C:31]([C:32]([C:2]2[CH:7]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:5]=[C:4]([F:15])[CH:3]=2)=[O:33])[CH:38]=[CH:39][C:40]=1[F:41])([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 236551051-Bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzeneHCID 594586793-((tert-Butyldimethylsilyl)oxy)-4-fluoro-N-methoxy-N-methylbenzamideHCID 178418339Butyllithium

Produkt 1

HCID 59458571(3-(Tert-butyldimethylsilyloxy)-4-fluorophenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanoneAusbeute 71 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3283Diethyl EtherLösungsmittel2×

Versuchsvorschrift

At −78° C. under argon, to a solution of 1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene (2.04 g, 7.01 mmol) in anhydrous ether (20 mL) was added nBuLi (3.5 mL, 2.0 M in cyclohexane, 7.0 mmol) dropwise and the reaction mixture was stirred for 1 h. 3-(Tert-butyldimethylsilyloxy)-4-fluoro-N-methoxy-N-methylbenzamide (2.00 g, 6.38 mmol) was added in one portion and the reaction mixture was stirred at −78° C. for 1.5 h. The pale yellow solution was poured into 1 N HCl aqueous solution (30 mL) and ether (30 mL) was used to rinse the reaction flask. The aqueous phase was separated and extracted with ether (20 mL). The combined ether portions were dried over Na2SO4, filtered and concentrated. The resulting oil was purified by ISCO chromatography (120 g column) using hexanes/EtOAc (0-100% over 30 min) to give (3-(tert-butyldimethylsilyloxy)-4-fluorophenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone at a retention time of 7 min (2.11 g, 71% yield). LCMS: RT=2.41 min [M+H] 465.19 (Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); NMR: 400 MHz 1H (CDCl3) 7.33 ppm, 3H, m; 7.28 ppm, 1H, m; 7.11 ppm, 2H, m; 5.86 ppm, 1H, t, J=53.39 Hz; 0.95 ppm, 9H, s; 0.15 ppm, 6H, s.

Aufarbeitung

  1. stirringthe reaction mixture was stirred at −78° C. for 1.5 h
  2. washto rinse the reaction flask
  3. customThe aqueous phase was separated
  4. extractionextracted with ether (20 mL)
  5. dry with materialThe combined ether portions were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting oil was purified by ISCO chromatography (120 g column)
  9. customhexanes/EtOAc (0-100% over 30 min)

Quellen und Nachweise

ORD-Eintrag
ord-7fe0554a59c146f0bf4ea5c02b9bc0c4
Quelldatensatz
uspto-grants-2010_09
Patentnummer
US07790770B2

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