Potassium Fluoride → HCID 68289383, compound

HRID 878750Notes

Reaction equation

HRID 878750 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[N:4][C:3]=1[N:12]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[CH:30][CH:29]=1)[S:13]([C:16]1[CH:26]=[CH:25][C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18][CH:17]=1)(=[O:15])=[O:14].C([Sn](CCCC)(CCCC)[C:44]([O:46]CC)=[CH2:45])CCC.[F-].[K+]>O1CCOCC1.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:44]([C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[N:4][C:3]=1[N:12]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[CH:30][CH:29]=1)[S:13]([C:16]1[CH:26]=[CH:25][C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18][CH:17]=1)(=[O:15])=[O:14])(=[O:46])[CH3:45]

Participants

7

Reactant 3

HCID 522689Potassium FluorideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 68289732HCID 68289732, compound

Product 1

HCID 68289383HCID 68289383, compoundYield 47%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of ethyl 4-({(4-bromoisoquinolin-3-yl)[4-(trifluoromethoxy)benzyl]amino}-sulfonyl)benzoate (122.0 mg, 0.20 mmol) prepared in Example 153, tributyl(1-ethoxyvinyl)tin (94.0 mg, 0.26 mmol) and dichlorobis(triphenylphosphine)palladium (II) (14.0 mg, 0.02 mmol) in 1,4-dioxane (1 mL) was heated to reflux under argon atmosphere for 16 hours. After cooling, the reaction solution was diluted with ethyl acetate, and poured into aqueous potassium fluoride solution. The mixture was stirred for 6 hours. The insoluble was filtered off, and then the filtrate was extracted with ethyl acetate. The organic layer was washed with water. Then, thereto was added 2 mol/L hydrochloric acid, and the mixture was stirred for 3 days. Then, the organic layer was separated, washed with water and saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=19:1→3:2) to give ethyl 4-({(4-acetylisoquinolin-3-yl) [4-(trifluoromethoxy)benzyl]amino}sulfonyl)benzoate (53.4 mg, 47%) as a white powder.

Workup

  1. temperaturewas heated
  2. temperatureto reflux under argon atmosphere for 16 hours
  3. temperatureAfter cooling
  4. filtrationThe insoluble was filtered off
  5. extractionthe filtrate was extracted with ethyl acetate
  6. washThe organic layer was washed with water
  7. additionThen, thereto was added 2 mol/L hydrochloric acid
  8. stirringthe mixture was stirred for 3 days
  9. customThen, the organic layer was separated
  10. washwashed with water and saturated brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. concentrationconcentrated under reduced pressure
  13. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=19:1→3:2)

Sources & evidence

ORD record
ord-dbd4cb50901949b08390532ab8401185
Source dataset
uspto-grants-2015_03
Patent number
US08987445B2

Reaction notes

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