Cesium carbonate → 5-(4-(difluoromethoxy)-3-methoxy-2-((3-(methoxymethyl)oxetan-3-yl)methoxy)phenyl)isobenzofuran-1(3H)-one

HRID 2171091Notes

Reaction equation

HRID 2171091 reaction equation
Br[C:2]1[C:7]([O:8][CH2:9][C:10]2([CH2:14][O:15][CH3:16])[CH2:13][O:12][CH2:11]2)=[C:6]([O:17][CH3:18])[C:5]([O:19][CH:20]([F:22])[F:21])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C(C)(C)OB([C:37]2[CH:38]=[C:39]3[C:43](=[CH:44][CH:45]=2)[C:42](=[O:46])[O:41][CH2:40]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:21][CH:20]([F:22])[O:19][C:5]1[CH:4]=[CH:3][C:2]([C:37]2[CH:38]=[C:39]3[C:43](=[CH:44][CH:45]=2)[C:42](=[O:46])[O:41][CH2:40]3)=[C:7]([O:8][CH2:9][C:10]2([CH2:14][O:15][CH3:16])[CH2:13][O:12][CH2:11]2)[C:6]=1[O:17][CH3:18]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 580746235-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3H-2-benzofuran-1-oneHCID 674676123-((6-Bromo-3-(difluoromethoxy)-2-methoxyphenoxy)methyl)-3-(methoxymethyl)oxetane

Product 1

HCID 674668085-(4-(difluoromethoxy)-3-methoxy-2-((3-(methoxymethyl)oxetan-3-yl)methoxy)phenyl)isobenzofuran-1(3H)-oneYield 12%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A stirring solution of 3-((6-bromo-3-(difluoromethoxy)-2-methoxyphenoxy)methyl)-3-(methoxymethyl)oxetane (220 mg, 0.574 mmol) in dimethylformamide (10 mL) was purged with argon for 1 h, to this cesium carbonate (561 mg, 1.72 mmol), tetrakis(triphenylphosphine) palladium(0) (19 mg, 0.017 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isobenzofuran-1(3H)-one (178 mg, 0.686 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 (30 mg, 12%).

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-aa44654842654b0682a05d720ecf3f37
Source dataset
uspto-grants-2015_06
Patent number
US09051290B2

Reaction notes

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