Water → 4-Chloro-5-ethyl-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinone

HRID 21313

Reaction equation

HRID 21313 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].[CH2:43]([Zn]CC)[CH3:44].C1(C)C=CC=CC=1.O>C(COC)OC>[Cl:1][C:2]1[C:10]([CH2:43][CH3:44])=[CH:9][C:8]([C:19]2[N:20]([C:35]([O:37][C:38]([CH3:41])([CH3:39])[CH3:40])=[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

5

Reactant 3

HCID 962WaterHCID 866283294-Chloro-5-trifluoromethanesulfonyloxy-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinoneHCID 178461639HCID 178461639, compound

Product 1

HCID 684909874-Chloro-5-ethyl-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinoneYield 52%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

4-Chloro-5-trifluoromethanesulfonyloxy-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinone (93.5 mg, 0.149 mmol) was dissolved in dimethoxyethane (4.7 mL), and the solution was added with 1.1 mmol/L diethyl zinc-toluene solution (0.68 mL, 0.744 mmol) and [bis(diphenylphosphino)ferrocene]dichloropalladium (34.4 mg, 0.030 mmol), followed by stirring at 90° C. for 12 hours under argon atmosphere. The reaction mixture was added with water and filtered using Celite. The filtrate was extracted with ethyl acetate. The organic layer was washed with saturated brine, followed by drying over 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-ethyl-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinone (39.0 mg, yield 52%).

Workup

  1. filtrationfiltered
  2. extractionThe filtrate was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialby drying over 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-511ca781d3724bffb5bb46b310d5c8f5
Source dataset
uspto-grants-2010_06
Patent number
US07745641B2

Linked notes

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