Cesium carbonate → HCID 67467518, compound

HRID 2171118Notes

Reaction equation

HRID 2171118 reaction equation
Br[C:2]1[C:7]([O:8][CH2:9][C:10]([NH:12][CH2:13][CH2:14][CH3:15])=[O:11])=[C:6]([O:16][CH3:17])[C:5]([O:18][CH:19]([F:21])[F:20])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C(C)(C)OB([C:36]2[CH:37]=[C:38]3[C:42](=[CH:43][CH:44]=2)[C:41](=[O:45])[NH:40][CH2:39]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:20][CH:19]([F:21])[O:18][C:5]1[C:6]([O:16][CH3:17])=[C:7]([C:2]([C:36]2[CH:37]=[C:38]3[C:42](=[CH:43][CH:44]=2)[C:41](=[O:45])[NH:40][CH2:39]3)=[CH:3][CH:4]=1)[O:8][CH2:9][C:10]([NH:12][CH2:13][CH2:14][CH3:15])=[O:11]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 219557955-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 67466578HCID 67466578, compound

Product 1

HCID 67467518HCID 67467518, compound

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A stirring solution of 2-(6-bromo-3-difluoromethoxy-2-methoxy-phenoxy)-N-propyl-acetamide (100 mg, 0.271 mmol) in dimethylformamide (10 mL) was purged with argon for 1 h, to this cesium carbonate (266 mg, 0.813 mmol), tetrakis(triphenylphosphine) palladium(0) (22 mg, 0.019 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (105.5 mg, 0.407 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. (20 mg, 18%).

Workup

  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 layer was 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)

Sources & evidence

ORD record
ord-bb716a56c30f4f40afc8972b214c2f63
Source dataset
uspto-grants-2015_06
Patent number
US09051290B2

Reaction notes

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