N-bromobutanimide → 5-Bromo-1'-methylspiro[indole-3,4'-piperidin]-2(1H)-one

HRID 661342Notes

Reaction equation

HRID 661342 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][C:5]2([C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9][C:8]2=[O:16])[CH2:4][CH2:3]1.C1C(=O)N([Br:24])C(=O)C1>CC#N.CO.C(OCC)(=O)C>[Br:24][C:13]1[CH:14]=[C:15]2[C:5]3([CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)[C:8](=[O:16])[NH:9][C:10]2=[CH:11][CH:12]=1

Participants

6

Reactant 2

HCID 67184N-bromobutanimideHCID 13837878HCID 13837878, compound

Product 1

HCID 457899295-Bromo-1'-methylspiro[indole-3,4'-piperidin]-2(1H)-oneYield 48.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1′-(methyl)spiro[indole-3,4′-piperidin]-2(1H)-one (6.3 g, 29.1 mmol) in CH3CN (100 ml) and MeOH (5 ml) was cooled to −5° C. and NBS (7.8 g, 44 mmol) was slowly added with stirring. The reaction mixture was stirred for 3.5 h at 0° C. Solvent was removed by vacuo. The residue was purified by silica gel chromatography (2-20% MeOH/CH2Cl2) to give 6 g as a solid. The solid compound was dissolved in ethyl acetate (600 ml) and washed with saturated aqueous NaHCO3 solution, dried (Na2SO4). Evaporation of the solvent in vacuo gave 4.2 g (47%) of 11. 1HNMR (CD3OD, 400 MHz) δ 7.51 (d, J=1.8 Hz, 1H), 7.35 (dd, J=1.9 and 8.2 Hz, 1H), 6.81 (d, J=8.2 Hz, 1H), 2.93 (m, 2H), 2.67 (m, 2H), 2.41 (s, 3H), 1.86 (m, 4H).

Workup

  1. stirringThe reaction mixture was stirred for 3.5 h at 0° C
  2. customSolvent was removed by vacuo
  3. customThe residue was purified by silica gel chromatography (2-20% MeOH/CH2Cl2)
  4. customto give 6 g as a solid
  5. washwashed with saturated aqueous NaHCO3 solution
  6. dry with materialdried (Na2SO4)
  7. customEvaporation of the solvent in vacuo

Sources & evidence

ORD record
ord-8935c4241be445dc8c573c0ce86ee01a
Source dataset
uspto-grants-2011_12
Patent number
US08084609B2

Reaction notes

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