Water → Carbonic acid 8-dimethylamino-1-methyl-2-oxo-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-4-yl ester ethyl ester

HRID 2367888Notes

Reaction equation

HRID 2367888 reaction equation
[CH3:1][N:2]([CH3:25])[N:3]1[CH2:24][CH2:23][C:6]2([N:10]([CH3:11])[C:9](=[O:12])[CH:8]([C:13]3[C:18]([CH3:19])=[CH:17][C:16]([CH3:20])=[CH:15][C:14]=3[CH3:21])[C:7]2=[O:22])[CH2:5][CH2:4]1.C(N(CC)CC)C.Cl[C:34]([O:36][CH2:37][CH3:38])=[O:35].O>O1CCCC1>[CH2:37]([O:36][C:34](=[O:35])[O:22][C:7]1[C:6]2([CH2:5][CH2:4][N:3]([N:2]([CH3:1])[CH3:25])[CH2:24][CH2:23]2)[N:10]([CH3:11])[C:9](=[O:12])[C:8]=1[C:13]1[C:18]([CH3:19])=[CH:17][C:16]([CH3:20])=[CH:15][C:14]=1[CH3:21])[CH3:38]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 672263978-Dimethylamino-1-methyl-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]decane-2,4-dione

Product 1

HCID 67225510Carbonic acid 8-dimethylamino-1-methyl-2-oxo-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-4-yl ester ethyl esterYield 86.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

105 mg 8-Dimethylamino-1-methyl-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]decane-2,4-dione (from Step 4) and 62 mg triethylamine are dissolved in 5 ml tetrahydrofuran, and the mixture cooled in an ice bath. Then, 40 mg ethyl chloroformate is added at 0° C. The mixture is allowed to warm to room temperature, and stirred for 2 hours. Then water is added and the mixture extracted with ethyl acetate. The organic layer is washed with brine, dried over sodium sulfate, and the solvent evaporated. The crude product is purified by chromatography on silica gel, with acetone as a solvent, yielding 110 mg Carbonic acid 8-dimethylamino-1-methyl-2-oxo-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-4-yl ester ethyl ester as an oil. 1H-NMR (CDCl3): 6.85 ppm (s, 2H), 4.03 ppm (q, 2H), 3.00 ppm (m, 2H), 2.96 ppm (s, 3H), 2.85 ppm (m, 2H), 2.42 ppm (s, 6H), 2.27 ppm (m, 2H), 2.24 ppm (s, 3H), 2.16 ppm (s, 2H), 1.83 ppm (m, 2H), 1.09 ppm (t, 3H).

Workup

  1. temperaturethe mixture cooled in an ice bath
  2. extractionthe mixture extracted with ethyl acetate
  3. washThe organic layer is washed with brine
  4. dry with materialdried over sodium sulfate
  5. customthe solvent evaporated
  6. customThe crude product is purified by chromatography on silica gel, with acetone as a solvent

Sources & evidence

ORD record
ord-9c258630ff854b779ada9233aa68fcbd
Source dataset
uspto-grants-2014_04
Patent number
US08703165B2

Reaction notes

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