(Z)-3-(Tributylstannyl)prop-2-en-1-ol → methyl 7-{N-[4-fluoro-2-((Z)-3-hydroxy-prop-1-enyl)-benzenesulfonyl]-N-(methoxycarbonyl)amino}-4H-furo[2,3-c]chromene-6-carboxylate

HRID 1778406Notes

Reaction equation

HRID 1778406 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([N:12]([C:17]1[C:26]([C:27]([O:29][CH3:30])=[O:28])=[C:25]2[C:20]([C:21]3[CH:33]=[CH:32][O:31][C:22]=3[CH2:23][O:24]2)=[CH:19][CH:18]=1)[C:13]([O:15][CH3:16])=[O:14])(=[O:11])=[O:10].C([Sn](CCCC)(CCCC)/[CH:39]=[CH:40]\[CH2:41][OH:42])CCC>O1CCOCC1.O>[F:8][C:6]1[CH:5]=[CH:4][C:3]([S:9]([N:12]([C:17]2[C:26]([C:27]([O:29][CH3:30])=[O:28])=[C:25]3[C:20]([C:21]4[CH:33]=[CH:32][O:31][C:22]=4[CH2:23][O:24]3)=[CH:19][CH:18]=2)[C:13]([O:15][CH3:16])=[O:14])(=[O:11])=[O:10])=[C:2](/[CH:39]=[CH:40]\[CH2:41][OH:42])[CH:7]=1

Participants

5

Reactant 2

HCID 9974944(Z)-3-(Tributylstannyl)prop-2-en-1-ol2×HCID 66685495methyl 7-{N-[2-bromo-4-fluorobenzenesulfonyl]-N-(methoxycarbonyl)amino}-4H-furo[2,3-c]chromene-6-carboxylate2×

Product 1

HCID 68093356methyl 7-{N-[4-fluoro-2-((Z)-3-hydroxy-prop-1-enyl)-benzenesulfonyl]-N-(methoxycarbonyl)amino}-4H-furo[2,3-c]chromene-6-carboxylateYield 78.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of methyl 7-{N-[2-bromo-4-fluorobenzenesulfonyl]-N-(methoxycarbonyl)amino}-4H-furo[2,3-c]chromene-6-carboxylate (Intermediate 93, 0.200 g) and (Z)-3-tributylstannanyl-prop-2-en-1-ol (Intermediate 1, 0.230 g) in dioxane (9 mL) and water (1 mL) was de-gassed and flushed with nitrogen. tris-(Dibenzylideneacetone)dipalladium (0.034 g) and tri-tert-butylphosphonium tetrafluoroborate (0.022 g) were added and the reaction mixture was heated to 70° C. for 30 minutes. The mixture was diluted with ethyl acetate and filtered. The filtrate was washed with water, dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, pre-equilibrated with ammonia solution in DCM, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 0-100%. The resultant product was triturated with ether to give methyl 7-{N-[4-fluoro-2((Z)-3-hydroxyprop-1-enyl)benzenesulfonyl]-N-(methoxycarbonyl)amino}-4H-furo[2,3-c]chromene-6-carboxylate (0.150 g) as a cream powder.

Workup

  1. customwas de-gassed
  2. customflushed with nitrogen
  3. additiontris-(Dibenzylideneacetone)dipalladium (0.034 g) and tri-tert-butylphosphonium tetrafluoroborate (0.022 g) were added
  4. additionThe mixture was diluted with ethyl acetate
  5. filtrationfiltered
  6. washThe filtrate was washed 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, pre-equilibrated with ammonia solution in DCM
  11. washeluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 0-100%
  12. customThe resultant product was triturated with ether

Sources & evidence

ORD record
ord-294bd64bb29d40bcba5de9c25b8383f5
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

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