Water → 6-Bromo-1′-methylspiro[3H-indole-3,4′-piperidin]-2(1H)-one

HRID 1619104Notes

Reaction equation

HRID 1619104 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Br:11][C:12]1[CH:20]=[C:19]2[C:15]([CH2:16][C:17](=[O:21])[NH:18]2)=[CH:14][CH:13]=1.Cl.Cl[CH2:24][CH2:25][N:26]([CH2:28][CH2:29]Cl)[CH3:27].O>O1CCCC1>[Br:11][C:12]1[CH:20]=[C:19]2[NH:18][C:17](=[O:21])[C:16]3([CH2:29][CH2:28][N:26]([CH3:27])[CH2:25][CH2:24]3)[C:15]2=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 962WaterHCID 5935Nitrogen mustard hydrochlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 27732896-bromo-2,3-dihydro-1H-indol-2-one

Product 1

HCID 497608716-Bromo-1′-methylspiro[3H-indole-3,4′-piperidin]-2(1H)-oneYield 31%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium bis(trimethylsilyl)amide (1.0M in tetrahydrofuran, 9.40 mL, 9.40 mmol) was added dropwise to a stirred suspension of 6-bromoindolin-2-one (preparation 1, 0.40 g, 1.89 mmol) in tetrahydrofuran (4 mL) at −78° C. The mixture was stirred for 30 minutes, then 2-chloro-N-(2-chloroethyl)-N-methylethanamine hydrochloride (0.36 g, 1.89 mmol) was added and the mixture was warmed to room temperature. After stirring overnight, water was added to the reaction and the mixture was extracted with ethyl acetate. The organic layer was dried (MgSO4) and evaporated. Purification of the residue by reverse phase chromatography (0% CH3CN in H2O to 100% CH3CN in H2O) gave the title compound as a yellow oil (0.17 g, 31%).

Workup

  1. stirringAfter stirring overnight
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialThe organic layer was dried (MgSO4)
  4. customevaporated
  5. customPurification of the residue by reverse phase chromatography (0% CH3CN in H2O to 100% CH3CN in H2O)

Sources & evidence

ORD record
ord-9493f6b56dde4d7299b36a2914512a1e
Source dataset
uspto-grants-2014_07
Patent number
US08772288B2

Reaction notes

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