Cesium carbonate → 5-(4-(difluoromethoxy)-3-methoxy-2-(methoxymethoxy)phenyl)isobenzofuran-1(3H)-one

HRID 2171079Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2171079
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:9]([F:11])[F:10])=[C:4]([O:12][CH3:13])[C:3]=1[O:14][CH2:15][O:16][CH3:17].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C(C)(C)OB([C:32]2[CH:33]=[C:34]3[C:38](=[CH:39][CH:40]=2)[C:37](=[O:41])[O:36][CH2:35]3)O1>CN(C)C=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:10][CH:9]([F:11])[O:8][C:5]1[CH:6]=[CH:7][C:2]([C:32]2[CH:33]=[C:34]3[C:38](=[CH:39][CH:40]=2)[C:37](=[O:41])[O:36][CH2:35]3)=[C:3]([O:14][CH2:15][O:16][CH3:17])[C:4]=1[O:12][CH3:13]

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 580746235-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3H-2-benzofuran-1-oneHCID 674667461-Bromo-4-(difluoromethoxy)-3-methoxy-2-(methoxymethoxy)benzene

Produkt 1

HCID 674678545-(4-(difluoromethoxy)-3-methoxy-2-(methoxymethoxy)phenyl)isobenzofuran-1(3H)-oneAusbeute 42,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A stirring solution of 1-bromo-4-(difluoromethoxy)-3-methoxy-2-(methoxymethoxy)benzene (3 g, 9.58 mmol) in N,N-dimethylformamide (30 mL) was purged with argon for 1 h, to this cesium carbonate (9.36 g, 28.74 mmol), tetrakis(triphenylphosphine) palladium(0) (553 mg, 0.479 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isobenzofuran-1(3H)-one (2.98 g, 11.49 mol) were added and the resultant reaction mixture was heated to 90° C. for 4 h. The reaction mixture was cooled to RT, filtered and the filtrate was diluted with water and extracted with ethyl acetate (3×). The combined ethyl acetate layers were washed with brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure. Purification of the residue by column chromatography (silica gel, 0-20% ethyl acetate in pet ether) afforded 5-(4-(difluoromethoxy)-3-methoxy-2-(methoxymethoxy)phenyl)isobenzofuran-1(3H)-one as a solid (1.5 g, 42%).

Aufarbeitung

  1. additionwere added
  2. customthe resultant reaction mixture
  3. temperatureThe reaction mixture was cooled to RT
  4. filtrationfiltered
  5. additionthe filtrate was diluted with water
  6. extractionextracted with ethyl acetate (3×)
  7. washThe combined ethyl acetate layers were washed with brine
  8. dry with materialdried over anhydrous sodium sulphate
  9. concentrationconcentrated under reduced pressure
  10. customPurification of the residue by column chromatography (silica gel, 0-20% ethyl acetate in pet ether)

Quellen und Nachweise

ORD-Eintrag
ord-431a9794816f4ee488616df8502aab12
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09051290B2

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