Cesium carbonate → Methyl 2,6-diamino-3-[2-(tert-butyldimethylsilanyloxymethyl)furan-3-yl]benzoate

HRID 927927Notes

Reaction equation

HRID 927927 reaction equation
Br[C:2]1[C:3]([NH2:13])=[C:4]([C:9]([NH2:12])=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[Si:14]([O:21][CH2:22][C:23]1[O:24][CH:25]=[CH:26][C:27]=1B(O)O)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].C(=O)([O-])[O-].[Cs+].[Cs+].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>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]>[NH2:13][C:3]1[C:2]([C:27]2[CH:26]=[CH:25][O:24][C:23]=2[CH2:22][O:21][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:15])[CH3:16])=[CH:11][CH:10]=[C:9]([NH2:12])[C:4]=1[C:5]([O:7][CH3:8])=[O:6]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 66685632Methyl 2,6-diamino-3-bromobenzoate2×HCID 709840592-(Tert-butyldimethylsilanyloxymethyl)furan-3-boronic acid2×

Product 1

HCID 90071951Methyl 2,6-diamino-3-[2-(tert-butyldimethylsilanyloxymethyl)furan-3-yl]benzoateYield 59.8%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
70 °C

Procedure

A mixture of methyl 3-bromo-2,6-diaminobenzoate (Intermediate 25, 2.6 g), 2-(tert-butyldimethylsilanyloxymethyl)furan-3-boronic acid (Intermediate 37, 3.5 g), cesium carbonate (11.35 g), tri-tert-butylphosphonium tetrafluoroborate (0.334 g) and tris-(dibenzylideneacetone)dipalladium (0.529 g) in dioxane (72 mL) and water (18 mL) was degassed and purged with nitrogen then heated at 70° C. for 75 minutes. After cooling, ethyl acetate and water were added and the mixture was filtered through Celite. The filtrate was separated and the organic layer was washed with brine, dried (MgSO4) 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 5-20% to give methyl 2,6-diamino-3-[2-(tert-butyldimethylsilanyloxymethyl)furan-3-yl]benzoate (2.39 g) as a viscous oil which was used without further characterization.

Workup

  1. customwas degassed
  2. custompurged with nitrogen
  3. temperatureAfter cooling
  4. additionethyl acetate and water were added
  5. filtrationthe mixture was filtered through Celite
  6. customThe filtrate was separated
  7. washthe organic layer was washed with brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customThe filtrate was evaporated to dryness
  11. customthe residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 5-20%

Sources & evidence

ORD record
ord-f97f597d5bf64360b34dfa84ab211726
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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