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

HRID 44136Notes

Reaction equation

HRID 44136 reaction equation
[CH3:1][N:2]([CH3:27])[N:3]1[C:7]2([CH2:12][CH2:11][N:10]([N:13]([CH3:15])[CH3:14])[CH2:9][CH2:8]2)[C:6](=[O:16])[CH:5]([C:17]2[C:22]([CH3:23])=[CH:21][C:20]([CH3:24])=[CH:19][C:18]=2[CH3:25])[C:4]1=[O:26].C(N(CC)CC)C.Cl[C:36]([O:38][CH2:39][CH3:40])=[O:37]>O1CCCC1>[CH2:39]([O:38][C:36](=[O:37])[O:16][C:6]1[C:7]2([CH2:12][CH2:11][N:10]([N:13]([CH3:14])[CH3:15])[CH2:9][CH2:8]2)[N:3]([N:2]([CH3:1])[CH3:27])[C:4](=[O:26])[C:5]=1[C:17]1[C:22]([CH3:23])=[CH:21][C:20]([CH3:24])=[CH:19][C:18]=1[CH3:25])[CH3:40]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 682286451,8-Bis-dimethylamino-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]decane-2,4-dione

Product 1

HCID 68228258Carbonic acid 1,8-bis-dimethylamino-2-oxo-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-4-yl ester ethyl esterYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

150 mg 1,8-Bis-dimethylamino-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]decane-2,4-dione (PREPARATION EXAMPLE 1) is dissolved in 3 ml tetrahydrofuran, 75 mg triethylamine is added, and the mixture is cooled to 0° C. 44 mg ethyl chloroformate is added and the resulting suspension stirred for 3 hours, thereby warming to room temperature. Then the mixture is partitioned between water and ethyl acetate, the organic layer separated and washed with brine, dried over anhydrous sodium sulfate, and evaporated. The residue is purified by chromatography on silica gel with ethyl acetate/heptane (1:1) as a solvent. Thus, 145 mg Carbonic acid 1,8-bis-dimethylamino-2-oxo-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-4-yl ester ethyl ester is obtained as a solid, mp 105° C. 1H-NMR (CDCl3): 6.83 ppm (s, 2H), 4.02 ppm (q, 2H), 3.05 ppm (m, 2H), 2.94 ppm (s, 6H), 2.80 ppm (m, 2H), 2.43 ppm (s, 6H), 2.40 ppm (m, 2H), 2.23 ppm (s, 3H), 2.17 ppm (s, 6H), 1.86 ppm (m, 2H), 1.08 ppm (t, 3H).

Workup

  1. temperaturewarming to room temperature
  2. customThen the mixture is partitioned between water and ethyl acetate
  3. customthe organic layer separated
  4. washwashed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated
  7. customThe residue is purified by chromatography on silica gel with ethyl acetate/heptane (1:1) as a solvent

Sources & evidence

ORD record
ord-42a0a72d026b4f8f8fc5d557b54924f3
Source dataset
uspto-grants-2013_09
Patent number
US08541343B2

Reaction notes

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