Cesium fluoride → methyl 3-bromo-6-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylmethyl]-2-methoxybenzoate

HRID 1778388Notes

Reaction equation

HRID 1778388 reaction equation
[Br:1][C:2]1[C:3]([O:24][CH3:25])=[C:4]([C:9]([CH2:12][S:13]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=2Br)(=[O:15])=[O:14])=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[CH2:26]([N:28]([CH2:45][CH3:46])[CH2:29]/[CH:30]=[CH:31]\[Sn](CCCC)(CCCC)CCCC)[CH3:27].[F-].[Cs+]>C1COCC1>[Br:1][C:2]1[C:3]([O:24][CH3:25])=[C:4]([C:9]([CH2:12][S:13]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=2/[CH:31]=[CH:30]\[CH2:29][N:28]([CH2:45][CH3:46])[CH2:26][CH3:27])(=[O:15])=[O:14])=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 66685956Methyl 3-bromo-6-(2-bromo-4-fluorobenzenesulfonylmethyl)-2-methoxybenzoate2×HCID 86684726N,N-diethyl-N-((Z)-1-tributylstannanylprop-1-en-3-yl)amine2×

Product 1

HCID 66693679methyl 3-bromo-6-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylmethyl]-2-methoxybenzoateYield 62.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of methyl 3-bromo-6-(2-bromo-4-fluorobenzenesulfonylmethyl)-2-methoxybenzoate (Intermediate 70, 5.85 g), N,N-diethyl-N-((Z)-1-tributylstannanylprop-1-en-3-yl)-amine (Intermediate 3, 5.00 g) and cesium fluoride (3.29 g) in THF (100 mL) was de-gassed and purged with nitrogen for 5 minutes. Palladium tetrakis-(triphenylphosphine) (0.720 g) was added and the reaction mixture was heated at reflux overnight. The mixture was cooled, diluted with ethyl acetate, filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica, eluting with a mixture of 2M ammonia in methanol and DCM, with a gradient of 0-10% to give methyl 3-bromo-6-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylmethyl]-2-methoxybenzoate (3.9 g) as an oil.

Workup

  1. customwas de-gassed
  2. custompurged with nitrogen for 5 minutes
  3. additionPalladium tetrakis-(triphenylphosphine) (0.720 g) was added
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux overnight
  6. temperatureThe mixture was cooled
  7. additiondiluted with ethyl acetate
  8. filtrationfiltered through Celite
  9. concentrationthe filtrate was concentrated in vacuo
  10. customThe residue was purified by chromatography on silica
  11. washeluting with a mixture of 2M ammonia in methanol and DCM, with a gradient of 0-10%

Sources & evidence

ORD record
ord-9ff57970ecaf4a24a360d0e7585d2224
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

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