Hydrochloric Acid → 8-Dimethylamino-1-methyl-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]decane-2,4-dione

HRID 2367887Notes

Reaction equation

HRID 2367887 reaction equation
C[O:2][C:3]([C:5]1([N:14]([CH3:27])[C:15](=[O:26])[CH2:16][C:17]2[C:22]([CH3:23])=[CH:21][C:20]([CH3:24])=[CH:19][C:18]=2[CH3:25])[CH2:10][CH2:9][N:8]([N:11]([CH3:13])[CH3:12])[CH2:7][CH2:6]1)=O.CC(C)([O-])C.[K+].[Cl-].[NH4+].Cl>CN(C)C=O>[CH3:12][N:11]([CH3:13])[N:8]1[CH2:7][CH2:6][C:5]2([N:14]([CH3:27])[C:15](=[O:26])[CH:16]([C:17]3[C:18]([CH3:25])=[CH:19][C:20]([CH3:24])=[CH:21][C:22]=3[CH3:23])[C:3]2=[O:2])[CH2:10][CH2:9]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 23665647Potassium tert-butoxideHCID 672257031-Dimethylamino-4-{methyl-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester

Product 1

HCID 672263978-Dimethylamino-1-methyl-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]decane-2,4-dioneYield 30.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
3 °C

Procedure

750 mg 1-Dimethylamino-4-{methyl-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester (from Step 3) is dissolved in 35 ml N,N-dimethylformamide, cooled in an ice bath to 3° C., and 672 mg potassium t-butoxide is added. The mixture is allowed to warm to room temperature and stirred for 18 hours. Then half saturated aqueous ammonium chloride solution is added, and the pH adjusted to 5.5 by the addition of aqueous hydrochloric acid. The mixture is extracted with ethyl acetate, the organic layer washed with brine, dried over sodium sulfate, and the solvent evaporated. The residue is purified by chromatography on silica gel, with ethyl acetate as a solvent. Thus, 210 mg 8-Dimethylamino-1-methyl-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]decane-2,4-dione is obtained as a solid, mp>195° C. 1H-NMR (CDCl3): 6.86 ppm (s, 2H), 3.12 ppm (m, 2H), 2.86 ppm (s, 3H), 2.84 ppm (m, 2H), 2.42 ppm (s, 6H), 2.30 ppm (m, 2H), 2.23 ppm (s, 3H), 2.17 ppm (s, 6H), 1.85 ppm (m, 2H).

Workup

  1. temperatureto warm to room temperature
  2. extractionThe mixture is extracted with ethyl acetate
  3. washthe organic layer washed with brine
  4. dry with materialdried over sodium sulfate
  5. customthe solvent evaporated
  6. customThe residue is purified by chromatography on silica gel, with ethyl acetate as a solvent

Sources & evidence

ORD record
ord-22aefdab7b444bc4a97db5536b346148
Source dataset
uspto-grants-2014_04
Patent number
US08703165B2

Reaction notes

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