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

HRID 2171172Notes

Reaction equation

HRID 2171172 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([O:10][CH:11]([F:13])[F:12])[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:12][CH:11]([F:13])[O:10][C:4]1[C:3]([O:14][CH2:15][O:16][CH3:17])=[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)[CH:7]=[CH:6][C:5]=1[O:8][CH3:9]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 580746235-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3H-2-benzofuran-1-oneHCID 67465272HCID 67465272, compound

Product 1

HCID 674635915-(3-(Difluoromethoxy)-4-methoxy-2-(methoxymethoxy)phenyl)isobenzofuran-1(3H)-oneYield 57%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A stirring solution of 1-bromo-3-(difluoromethoxy)-4-methoxy-2-(methoxymethoxy)benzene (1.5 g, 4.79 mmol) in dimethylformamide (30 mL) was purged with argon gas for 1 h, to this cesium carbonate (4.7 g, 14.37 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 (1.49 g, 5.74 mmol) were added and the resultant reaction mixture was heated to 80° 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-(3-(Difluoromethoxy)-4-methoxy-2-(methoxymethoxy)phenyl)isobenzofuran-1(3H)-one as a solid (1 g, 56.8%).

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 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)

Sources & evidence

ORD record
ord-b3e906a81f5e40cf88f4b62846580e7c
Source dataset
uspto-grants-2015_06
Patent number
US09051290B2

Reaction notes

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