Cesium carbonate → Methyl 6-amino-3-(2-formylfuran-3-yl)-2-hydroxybenzoate

HRID 1778353Notes

Reaction equation

HRID 1778353 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([OH:12])[C:5](Br)=[CH:4][CH:3]=1.[CH:14]([C:16]1[O:17][CH:18]=[CH:19][C:20]=1B1OC(C)(C)C(C)(C)O1)=[O:15].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([OH:12])[C:5]([C:20]2[CH:19]=[CH:18][O:17][C:16]=2[CH:14]=[O:15])=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 164141993-(Tetramethyl-1,3,2-dioxaborolan-2-yl)furan-2-carbaldehydeHCID 66685945Methyl 6-amino-3-bromo-2-hydroxybenzoate

Product 1

HCID 86684733Methyl 6-amino-3-(2-formylfuran-3-yl)-2-hydroxybenzoateYield 88%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of methyl 6-amino-3-bromo-2-hydroxybenzoate (prepared according to Wang et al, Bioorg Med Chem Lett 2007 17 2817, 1.84 g), 2-formylfuran-3-boronic acid pinacol ester (1.99 g), tri-tert-butylphosphinium tetrafluoroborate (0.218 g), cesium carbonate (7.33 g) and tris-(dibenzylideneacetone)dipalladium (0.343 g) in dioxane (75 mL) and water (9.4 mL) was heated at 65° C., under nitrogen, for 1 hour. After cooling, the mixture was diluted with ethyl acetate and water and the organic layer was separated, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 10-50% to give methyl 6-amino-3-(2-formylfuran-3-yl)-2-hydroxybenzoate (1.72 g) as a yellow solid. The material was used without further characterisation.

Workup

  1. temperatureAfter cooling
  2. customthe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customThe filtrate was evaporated to dryness
  6. customthe residue was purified by chromatography on silica
  7. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 10-50%

Sources & evidence

ORD record
ord-c675ffeb7dbf4b29ba1aee45bda401f7
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

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