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

HRID 1778383Notes

Reaction equation

HRID 1778383 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[C:6]([OH:15])[C:5](Br)=[CH:4][CH:3]=1.[CH:17]([C:19]1[O:20][CH:21]=[CH:22][C:23]=1B1OC(C)(C)C(C)(C)O1)=[O:18].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.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][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[C:6]([OH:15])[C:5]([C:23]2[CH:22]=[CH:21][O:20][C:19]=2[CH:17]=[O:18])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 164141993-(Tetramethyl-1,3,2-dioxaborolan-2-yl)furan-2-carbaldehydeHCID 66685946Tert-butyl 6-amino-3-bromo-2-hydroxybenzoate2×

Product 1

HCID 86684736Tert-butyl 6-amino-3-(2-formylfuran-3-yl)-2-hydroxybenzoateYield 69.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of tert-butyl 6-amino-3-bromo-2-hydroxybenzoate (Intermediate 62, 1.16 g), 2-formylfuran-3-boronic acid pinacol ester (1.073 g), tris-(dibenzylideneacetone)dipalladium (0.184 g), tri-tert-butylphosphonium tetrafluoroborate (0.117 g) and cesium carbonate (3.935 g) was suspended in dioxane (40 mL) and water (5 mL). The mixture was de-gassed and flushed with nitrogen then heated at 70° C. for 3 hours. After cooling, the mixture was concentrated in vacuo. The residue was partitioned between water and ethyl acetate and the combined organic layers were dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 2.5-25% to give tert-butyl 6-amino-3-(2-formylfuran-3-yl)-2-hydroxybenzoate (0.854 g) as a yellow oil.

Workup

  1. customThe mixture was de-gassed
  2. customflushed with nitrogen
  3. temperatureAfter cooling
  4. concentrationthe mixture was concentrated in vacuo
  5. customThe residue was partitioned between water and ethyl acetate
  6. dry with materialthe combined organic layers were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by chromatography on silica
  10. washeluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 2.5-25%

Sources & evidence

ORD record
ord-9060a67989b84c98844290231f824fb5
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

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