Ammonium fluoride → 4-Chloro-5-(2-furyl)-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinone

HRID 21312

Reaction equation

HRID 21312 reaction equation
[Cl:1][C:2]1[C:10](OS(C(F)(F)F)(=O)=O)=[CH:9][C:8]([C:19]2[N:20]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C:21]3[C:26]([CH:27]=2)=[CH:25][C:24]([CH2:28][N:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)=[CH:23][CH:22]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:42].C([Sn](CCCC)(CCCC)[C:48]1[O:49][CH:50]=[CH:51][CH:52]=1)CCC.[Cl-].[Li+].[F-].[NH4+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[C:10]([C:48]2[O:49][CH:50]=[CH:51][CH:52]=2)=[CH:9][C:8]([C:19]2[N:20]([C:35]([O:37][C:38]([CH3:39])([CH3:40])[CH3:41])=[O:36])[C:21]3[C:26]([CH:27]=2)=[CH:25][C:24]([CH2:28][N:29]2[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]2)=[CH:23][CH:22]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:42]

Participants

7

Reactant 4

HCID 25516Ammonium fluorideHCID 433294Lithium ChlorideHCID 43936882-(Tributylstannyl)furanHCID 866283294-Chloro-5-trifluoromethanesulfonyloxy-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinone

Product 1

HCID 684873464-Chloro-5-(2-furyl)-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinoneYield 60.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

4-Chloro-5-trifluoromethanesulfonyloxy-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinone (100 mg, 0.159 mmol) was dissolved in 1,4-dioxane (3.0 mL), and the solution was added with 2-(tributylstannyl)furan (0.150 mL, 0.477 mmol), tetrakis(triphenylphosphine)palladium (15.0 mg, 0.0130 mmol) and lithium chloride (60.6 mg, 1.43 mmol), followed by stirring at 90° C. for 6.0 hours under argon atmosphere. The reaction mixture was added with 10% aqueous ammonium fluoride solution and filtered using Celite. The filtrate was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by preparative thin-layer chromatography (chloroform/methanol=6/1) to obtain 4-chloro-5-(2-furyl)-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinone (52.2 mg, yield 60%).

Workup

  1. filtrationfiltered
  2. extractionThe filtrate was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by preparative thin-layer chromatography (chloroform/methanol=6/1)

Sources & evidence

ORD record
ord-c6905c7eb97e4bdb8122dce196f0807e
Source dataset
uspto-grants-2010_06
Patent number
US07745641B2

Linked notes

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