Hexane → (4-Fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone

HRID 238883

Reaktionsgleichung

Reaktionsgleichung von HRID 238883
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.[F:16][C:17]1[CH:28]=[CH:27][C:20]([C:21](N(OC)C)=[O:22])=[CH:19][C:18]=1[O:29][CH:30]([CH3:32])[CH3:31].[Li]CCCC.CCCCCC>C1COCC1>[F:16][C:17]1[CH:28]=[CH:27][C:20]([C:21]([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:22])=[CH:19][C:18]=1[O:29][CH:30]([CH3:32])[CH3:31]

Komponenten

6

Edukt 4

HCID 8058HexaneHCID 236551051-Bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzeneHCID 59459043Benzamide,4-fluoro-N-methoxy-N-methyl-3-(1-methylethoxy)-HCID 178418339Butyllithium

Produkt 1

HCID 59459304(4-Fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-76 °C

Versuchsvorschrift

A 3-liter four neck round-bottomed flask (flame dried) was charged 1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene (72.88 g, 0.25 mol), 4-fluoro-3-isopropoxy-N-methoxy-N-methylbenzamide (60.39 g, 0.25 mol) and dry THF (700 mL) under N2. The solution was cooled to −76° C., and a solution of n-BuLi in hexane (2.5M, 100 mL, 0.25 mol) was drop-wise maintaining the reaction mixture temperature below −70° C. over a period of 40 min. The reaction mixture was stirred at −76° C. for 1.5 h then quenched with 1N HCl (500 mL). The mixture was concentrated in vacuo to half the volume and was partitioned between EtOAc and H2O (v/v 1:0.3, 1 L). The organic phase was separated and the aqueous layer was extracted with EtOAc (500 mL). The combined organic extracts were washed with brine and then concentrated in vacuo to give a yellow oil which was purified by column chromatography using CH2Cl2 in hexanes (0% to 20%) to give (4-fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone as a colorless oil contaminated with a by-product (49.0 g, 50%). LC-MS (10-90% MeOH in H2O with 0.1% TFA in a 2-min gradient) 393.2 (M+H), retention time=2.15 min.

Aufarbeitung

  1. customthen quenched with 1N HCl (500 mL)
  2. concentrationThe mixture was concentrated in vacuo to half the volume
  3. customwas partitioned between EtOAc and H2O (v/v 1:0.3, 1 L)
  4. customThe organic phase was separated
  5. extractionthe aqueous layer was extracted with EtOAc (500 mL)
  6. washThe combined organic extracts were washed with brine
  7. concentrationconcentrated in vacuo
  8. customto give a yellow oil which
  9. customwas purified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-0e10d4bce98b403587dc6fd0c1d1c137
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642576B2

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