Cesium carbonate → HCID 67465024, compound

HRID 2171102Notes

Reaction equation

HRID 2171102 reaction equation
Br[C:2]1[C:7]([O:8][CH2:9][C:10]([CH3:14])([CH3:13])[CH2:11][OH:12])=[C:6]([O:15][CH3:16])[C:5]([O:17][CH:18]([F:20])[F:19])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C(C)(C)OB([C:35]2[CH:36]=[C:37]3[C:41](=[CH:42][CH:43]=2)[C:40](=[O:44])[NH:39][CH2:38]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:19][CH:18]([F:20])[O:17][C:5]1[CH:4]=[CH:3][C:2]([C:35]2[CH:36]=[C:37]3[C:41](=[CH:42][CH:43]=2)[C:40](=[O:44])[NH:39][CH2:38]3)=[C:7]([O:8][CH2:9][C:10]([CH3:14])([CH3:13])[CH2:11][OH:12])[C:6]=1[O:15][CH3:16]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 219557955-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 67466678HCID 67466678, compound

Product 1

HCID 67465024HCID 67465024, compound

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a stirring solution of 3-(6-bromo-3-(difluoromethoxy)-2-methoxyphenoxy)-2,2-dimethylpropan-1-ol (200 mg, 0.563 mmol) in dimethylformamide (10 mL) was purged with argon for 1 h. To this cesium carbonate (548 mg, 1.689 mmol), tetrakis(triphenylphosphine) palladium(0) (32 mg, 0.028 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (175 mg, 0.675 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 (50 mg, 22%).

Workup

  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)

Sources & evidence

ORD record
ord-beb92ee0f7f24aeaafd1c72d0b962e53
Source dataset
uspto-grants-2015_06
Patent number
US09051290B2

Reaction notes

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