Cesium carbonate → Ethyl 4-(2,4-diamino-3-methoxycarbonylphenyl)-furan-3-carboxylate

HRID 1778403Notes

Reaction equation

HRID 1778403 reaction equation
[NH2:1][C:2]1[C:11](Br)=[CH:10][CH:9]=[C:8]([NH2:13])[C:3]=1[C:4]([O:6][CH3:7])=[O:5].COC([C:18]1[O:19][CH:20]=[CH:21][C:22]=1B(O)O)=O.F[B-](F)(F)F.C([PH+]([C:40]([CH3:43])(C)C)C(C)(C)C)(C)(C)C.[C:44](=O)([O-:46])[O-:45].[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:3]([C:4]([O:6][CH3:7])=[O:5])=[C:8]([NH2:13])[CH:9]=[CH:10][C:11]=1[C:21]1[C:22]([C:44]([O:46][CH2:40][CH3:43])=[O:45])=[CH:18][O:19][CH:20]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 66685498[2-(Methoxycarbonyl)furan-3-yl]boronic acidHCID 66685632Methyl 2,6-diamino-3-bromobenzoate2×

Product 1

HCID 66685491Ethyl 4-(2,4-diamino-3-methoxycarbonylphenyl)-furan-3-carboxylateYield 689.8%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of methyl 2,6-diamino-3-bromobenzoate (Intermediate 90, 1.0 g), 2-methoxycarbonyl-furan-3-boronic acid (0.980 g), tris-(dibenzylideneacetone)-dipalladium (0.188 g), tri-tert-butylphosphonium tetrafluoroborate (0.119 g) and cesium carbonate (4.0 g) in dioxane (45 mL) and water (6 mL) was de-gassed and flushed with argon. The resultant mixture was stirred at room temperature for 1 hour, then heated at 70° C. for 1 hour. The mixture was cooled, diluted with ethyl acetate and washed with water, 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 pentane, with a gradient of 20-50% to give ethyl 4-(2,4-diamino-3-methoxycarbonylphenyl)-furan-3-carboxylate (0.861 g).

Workup

  1. customwas de-gassed
  2. customflushed with argon
  3. temperatureheated at 70° C. for 1 hour
  4. temperatureThe mixture was cooled
  5. additiondiluted with ethyl acetate
  6. washwashed with water
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe residue was purified by chromatography on silica
  11. washeluting with a mixture of ethyl acetate and pentane, with a gradient of 20-50%

Sources & evidence

ORD record
ord-52135b162fed41f4b890d3e57a9629fe
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

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