Cesium carbonate → 4-((3-(Difluoromethoxy)-2-methoxy-6-(1-oxoisoindolin-5-yl)phenoxy)methyl)benzamide

HRID 2171114Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2171114
Br[C:2]1[C:7]([O:8][CH2:9][C:10]2[CH:18]=[CH:17][C:13]([C:14]([NH2:16])=[O:15])=[CH:12][CH:11]=2)=[C:6]([O:19][CH3:20])[C:5]([O:21][CH:22]([F:24])[F:23])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C(C)(C)OB([C:39]2[CH:40]=[C:41]3[C:45](=[CH:46][CH:47]=2)[C:44](=[O:48])[NH:43][CH2:42]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:23][CH:22]([F:24])[O:21][C:5]1[C:6]([O:19][CH3:20])=[C:7]([C:2]([C:39]2[CH:40]=[C:41]3[C:45](=[CH:46][CH:47]=2)[C:44](=[O:48])[NH:43][CH2:42]3)=[CH:3][CH:4]=1)[O:8][CH2:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([NH2:16])=[O:15])=[CH:12][CH:11]=1

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 219557955-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 674639064-((6-Bromo-3-(difluoromethoxy)-2-methoxyphenoxy)methyl)benzamide

Produkt 1

HCID 674655434-((3-(Difluoromethoxy)-2-methoxy-6-(1-oxoisoindolin-5-yl)phenoxy)methyl)benzamideAusbeute 17,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a stirring solution of 4-((6-bromo-3-(difluoromethoxy)-2-methoxyphenoxy)methyl)benzamide (500 mg, 1.24 mmol) in dimethylformamide (10 mL) was purged with argon for 1 h. To this cesium carbonate (1.2 g, 3.73 mmol), tetrakis(triphenylphosphine) palladium(0) (72 mg, 0.06 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (386 mg, 1.49 mmol) were added and the resultant reaction mixture was heated to 80-90° C. for 3 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 layer was washed with brine and 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 the title compound as a solid (100 mg, 17.7%).

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-a6502d2f25034ddc9fdca096117e37ca
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09051290B2

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