Cesium carbonate → Methyl 6-amino-3-[2-(tert-butyldimethylsilanyloxymethyl)-4-fluoro-5-trimethylsilanylfuran-3-yl]-2-hydroxybenzoate

HRID 1778414Notes

Reaction equation

HRID 1778414 reaction equation
[Si:1]([O:8][CH2:9][C:10]1[O:11][C:12]([Si:19]([CH3:22])([CH3:21])[CH3:20])=[C:13]([F:18])[C:14]=1B(O)O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[NH2:23][C:24]1[C:29]([C:30]([O:32][CH3:33])=[O:31])=[C:28]([OH:34])[C:27](Br)=[CH:26][CH:25]=1.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.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]>[NH2:23][C:24]1[C:29]([C:30]([O:32][CH3:33])=[O:31])=[C:28]([OH:34])[C:27]([C:14]2[C:13]([F:18])=[C:12]([Si:19]([CH3:22])([CH3:21])[CH3:20])[O:11][C:10]=2[CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])=[CH:26][CH:25]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 66685945Methyl 6-amino-3-bromo-2-hydroxybenzoateHCID 666863202-(Tert-butyldimethylsilanyloxymethyl)-4-fluoro-5-trimethylsilanylfuran-3-yl-boronic acid2×

Product 1

HCID 66693194Methyl 6-amino-3-[2-(tert-butyldimethylsilanyloxymethyl)-4-fluoro-5-trimethylsilanylfuran-3-yl]-2-hydroxybenzoateYield 47.6%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
63 °C

Procedure

A mixture of 2-(tert-butyldimethylsilanyloxymethyl)-4-fluoro-5-trimethylsilanylfuran-3-yl-boronic acid (Intermediate 103, 6.0 g), methyl 6-amino-3-bromo-2-hydroxybenzoate (prepared according to Wang et al, Bioorg Med Chem Lett 2007 17 2817, 4.27 g), tris-(dibenzylideneacetone)dipalladium (0.793 g), tri-tert-butylphosphonium tetrafluoroborate (0.502 g) and cesium carbonate (16.94 g) in dioxane (96 mL) and water (12 mL) was heated at 63° C., under an atmosphere of nitrogen for 90 minutes. The mixture was cooled and diluted with ethyl acetate, washed with water, dried (Na2SO4) 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 0-20%. The resultant product was re-purified by chromatography on silica, eluting with a mixture of DCM and cyclohexane, with a gradient of 0-100% to give methyl 6-amino-3-[2-(tert-butyldimethylsilanyloxymethyl)-4-fluoro-5-trimethylsilanylfuran-3-yl]-2-hydroxybenzoate (3.86 g) as a yellow oil which crystallised with scratching to give an off-white solid.

Workup

  1. temperatureThe mixture was cooled
  2. washwashed with water
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by chromatography on silica
  7. washeluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 0-20%
  8. customThe resultant product was re-purified by chromatography on silica
  9. washeluting with a mixture of DCM and cyclohexane, with a gradient of 0-100%

Sources & evidence

ORD record
ord-4d214c5f0f7045f19b5cdb0329a364d3
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

Loading…