Water → HCID 67225706, compound

HRID 2367883Notes

Reaction equation

HRID 2367883 reaction equation
[CH3:1][N:2]([CH3:24])[N:3]1[CH2:23][CH2:22][C:6]2([NH:10][C:9](=[O:11])[CH:8]([C:12]3[C:17]([CH3:18])=[CH:16][C:15]([CH3:19])=[CH:14][C:13]=3[CH3:20])[C:7]2=[O:21])[CH2:5][CH2:4]1.C(N(CC)CC)C.Cl[C:33]([O:35][CH2:36][CH3:37])=[O:34].O>O1CCCC1>[CH2:36]([O:35][C:33](=[O:34])[O:21][C:7]1[C:6]2([CH2:5][CH2:4][N:3]([N:2]([CH3:1])[CH3:24])[CH2:23][CH2:22]2)[NH:10][C:9](=[O:11])[C:8]=1[C:12]1[C:13]([CH3:20])=[CH:14][C:15]([CH3:19])=[CH:16][C:17]=1[CH3:18])[CH3:37]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 67225432HCID 67225432, compound

Product 1

HCID 67225706HCID 67225706, compoundYield 66.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

97 mg 8-Dimethylamino-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]decane-2,4-dione (from Step 4) and 45 mg triethylamine are dissolved in 15 ml tetrahydrofuran, and the mixture cooled in an ice bath. Then, 33 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 ethyl acetate/methanol/triethylamine (90:5:5) as a solvent, yielding 79 mg Carbonic acid 8-dimethylamino-2-oxo-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-4-yl ester ethyl ester as a solid, mp 162-166° C. 1H-NMR (CDCl3): 7.20 ppm (s, broad, 1H), 6.83 ppm (s, 2H), 4.02 ppm (q, 2H), 3.05 ppm (m, 2H), 2.54 ppm (m, 2H), 2.40 ppm (s, 6H), 2.25 ppm (m, 5H), 2.17 ppm (s, 6H), 1.70 ppm (m, 2H), 1.10 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 ethyl acetate/methanol/triethylamine (90:5:5) as a solvent

Sources & evidence

ORD record
ord-c3f0a6507b8343a5b8b3fb73102a5c6a
Source dataset
uspto-grants-2014_04
Patent number
US08703165B2

Reaction notes

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