Acetic Acid → 4-Chloro-7-[1-(tert-butoxycarbonyl)-5-(4-bromopiperidinomethyl)indol-2-yl]isoindolinone

HRID 21031

Reaction equation

HRID 21031 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH:20]=O)=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:29].Br.[Br:31][CH:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.O>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:22]([O:24][C:25]([CH3:28])([CH3:26])[CH3:27])=[O:23])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH2:20][N:35]2[CH2:36][CH2:37][CH:32]([Br:31])[CH2:33][CH2:34]2)=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:29]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 10340Sodium CarbonateHCID 27346764-Bromopiperidine HydrobromideHCID 5049666Sodium triacetoxyborohydrideHCID 866282274-Chloro-7-[1-(tert-butoxycarbonyl)-5-formylindol-2-yl]isoindolinone

Product 1

HCID 684909894-Chloro-7-[1-(tert-butoxycarbonyl)-5-(4-bromopiperidinomethyl)indol-2-yl]isoindolinoneYield 133%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

In a similar manner to Step 2 of Example 6, 4-chloro-7-[1-(tert-butoxycarbonyl)-5-formylindol-2-yl]isoindolinone (42.7 mg, 0.104 mmol) was dissolved in acetonitrile (2 mL), and the solution was treated with 4-bromopiperidine hydrobromide (105 mg, 0.428 mmol), acetic acid (0.120 mL, 2.10 mmol) and sodium triacetoxyborohydride (51.1 mg, 0.241 mmol). The reaction mixture was added with water and sodium carbonate to adjust the pH to 9. The mixture 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 to obtain 4-chloro-7-[1-(tert-butoxycarbonyl)-5-(4-bromopiperidinomethyl)indol-2-yl]isoindolinone (77.3 mg).

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-33868e70b9c74e32b9f919f941c27714
Source dataset
uspto-grants-2010_06
Patent number
US07745641B2

Linked notes

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