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

HRID 44135Notes

Reaction equation

HRID 44135 reaction equation
C[O:2][C:3]([C:5]1([N:14]([C:18](=[O:29])[CH2:19][C:20]2[C:25]([CH3:26])=[CH:24][C:23]([CH3:27])=[CH:22][C:21]=2[CH3:28])[N:15]([CH3:17])[CH3:16])[CH2:10][CH2:9][N:8]([N:11]([CH3:13])[CH3:12])[CH2:7][CH2:6]1)=O.CC(C)([O-])C.[K+].[OH-].[NH4+].Cl>CN(C)C=O>[CH3:17][N:15]([CH3:16])[N:14]1[C:5]2([CH2:10][CH2:9][N:8]([N:11]([CH3:12])[CH3:13])[CH2:7][CH2:6]2)[C:3](=[O:2])[CH:19]([C:20]2[C:21]([CH3:28])=[CH:22][C:23]([CH3:27])=[CH:24][C:25]=2[CH3:26])[C:18]1=[O:29]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14923Ammonium HydroxideHCID 23665647Potassium tert-butoxideHCID 672274551-Dimethylamino-4-{N',N'-dimethyl-N-[2-(2,4,6-trimethyl-phenyl)-acetyl]-hydrazino}-piperidine-4-carboxylic acid methyl ester

Product 1

HCID 682286451,8-Bis-dimethylamino-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]decane-2,4-dioneYield 32.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Under an atmosphere of argon, a solution of 1.25 g 1-Dimethylamino-4-{N′,N′-dimethyl-N-[2-(2,4,6-trimethyl-phenyl)-acetyl]-hydrazino}-piperidine-4-carboxylic acid methyl ester in 10 ml dry N,N-dimethylformamide is cooled to 5° C., and treated with 1.04 g potassium t-butoxide. The mixture is stirred at ambient temperature for 18 hours, then poured into aqueous ammonium hydroxide, and the pH of the solution adjusted to 4.5 by the addition of aqueous hydrochloric acid. It is extracted three times with ethyl acetate, the organic layer separated, dried over sodium sulfate and evaporated. The residue is purified by chromatography on silica gel with cyclohexane/ethyl acetate (1:3) as a solvent, to yield 377 mg 1,8-Bis-dimethylamino-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]decane-2,4-dione as a solid, mp 80-85° C. 1H-NMR (methanol-d4): 6.91 ppm (s, 2H), 3.18 ppm (m, 2H), 3.08 ppm (m, 2H), 2.93 ppm (s, 6H), 2.48 ppm (s, 6H), 2.35 ppm (m, 2H), 2.29 ppm (s, 3H), 2.14 ppm (s, 6H), 1.40 ppm (m, 2H).

Workup

  1. extractionIt is extracted three times with ethyl acetate
  2. customthe organic layer separated
  3. dry with materialdried over sodium sulfate
  4. customevaporated
  5. customThe residue is purified by chromatography on silica gel with cyclohexane/ethyl acetate (1:3) as a solvent

Sources & evidence

ORD record
ord-41e8d41239dc4af2bcd41db91c2ec37a
Source dataset
uspto-grants-2013_09
Patent number
US08541343B2

Reaction notes

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