Cesium carbonate → 4-((3-(difluoromethoxy)-2-methoxy-6-(1-oxo-2,3-dihydro-1H-inden-4-yl)phenoxy)methyl)benzamide

HRID 2171078Notes

Reaction equation

HRID 2171078 reaction equation
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:47]=[CH:46][CH:45]=[C:44]3[C:40]=2[CH2:41][CH2:42][C:43]3=[O:48])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:47]=[CH:46][CH:45]=[C:44]3[C:40]=2[CH2:41][CH2:42][C:43]3=[O:48])=[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

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 220320882,3-Dihydro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-inden-1-oneHCID 674639064-((6-Bromo-3-(difluoromethoxy)-2-methoxyphenoxy)methyl)benzamide

Product 1

HCID 674680644-((3-(difluoromethoxy)-2-methoxy-6-(1-oxo-2,3-dihydro-1H-inden-4-yl)phenoxy)methyl)benzamideYield 26.7%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

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 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-one (641 mg, 2.48 mmol) was added and the resultant reaction mixture was heated to 80° C. for 16 h. The reaction mixture was cooled to RT and filtered through celite and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 0-80% ethyl acetate in pet ether) to afford title compound as a solid (150 mg, 26.7%).

Workup

  1. additionwas added
  2. customthe resultant reaction mixture
  3. temperatureThe reaction mixture was cooled to RT
  4. filtrationfiltered through celite
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by column chromatography (silica gel, 0-80% ethyl acetate in pet ether)

Sources & evidence

ORD record
ord-e16d07b40ae14a33b4ce8d496ec602cf
Source dataset
uspto-grants-2015_06
Patent number
US09051290B2

Reaction notes

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