Triethylamine → 8-(2-Chloronicotinoylcarbamoyl)-3-isopropyl-4-methylene-2-oxo-1-oxa-3,8-diazaspiro[4,5]decane

HRID 466609Notes

Reaction equation

HRID 466609 reaction equation
C(Cl)(=O)[C:2](Cl)=[O:3].[Cl:7][C:8]1[N:16]=[CH:15][CH:14]=[CH:13][C:9]=1[C:10]([NH2:12])=[O:11].C(N(CC)CC)C.[CH:24]([N:27]1[C:31](=[CH2:32])[C:30]2([CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[O:29][C:28]1=[O:38])([CH3:26])[CH3:25]>ClCCCl>[Cl:7][C:8]1[N:16]=[CH:15][CH:14]=[CH:13][C:9]=1[C:10]([NH:12][C:2]([N:35]1[CH2:36][CH2:37][C:30]2([O:29][C:28](=[O:38])[N:27]([CH:24]([CH3:26])[CH3:25])[C:31]2=[CH2:32])[CH2:33][CH2:34]1)=[O:3])=[O:11]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 825882-ChloronicotinamideHCID 198143423-Isopropyl-4-methylene-2-oxo-1-oxa-3,8-diazaspiro[4,5]decane

Product 1

HCID 198143638-(2-Chloronicotinoylcarbamoyl)-3-isopropyl-4-methylene-2-oxo-1-oxa-3,8-diazaspiro[4,5]decaneYield 54%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Conditions

Temperature
85 °C

Procedure

5.8 g of oxalyl chloride are portionwise added to the solution of 6.2 g of 2-chloronicotinic acid amide in 150 ml of anhydrous 1,2-dichloroethane under stirring, then the reaction mixture is heated at 85° C. for 90 minutes. After cooling the mixture to 0° to 5° C. first 12.6 ml of triethylamine and then a solution of 8.4 g of 3-isopropyl-4-methylene-2-oxo-1-oxa-3,8-diazaspiro[4,5]decane in 42 ml of anhydrous 1,2-dichloroethane are portionwise added while maintaining the temperature between 20° and 30° C. The reaction mixture is stirred at room temperature for an additional 30 minutes, then extracted with 200 ml of N sodium hydroxide solution and then with 100 ml of water. After combining the aqueous extract is acidified to a pH value of 5.5 to 6 by adding acetic acid and the mixture is extracted with 1,2-dichloroethane. The organic solution is washed with water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue is recrystallized from ethanol to give the title compound in 54% yield, m.p.: 186°-188° C.

Workup

  1. temperaturewhile maintaining the temperature between 20° and 30° C
  2. stirringThe reaction mixture is stirred at room temperature for an additional 30 minutes
  3. extractionextracted with 200 ml of N sodium hydroxide solution
  4. extractionaqueous extract
  5. additionby adding acetic acid
  6. extractionthe mixture is extracted with 1,2-dichloroethane
  7. washThe organic solution is washed with water
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customevaporated under reduced pressure
  10. customThe residue is recrystallized from ethanol

Sources & evidence

ORD record
ord-4118b8d934a54612bdaa903b7e808dc3
Source dataset
uspto-grants-1992_10
Patent number
US05157038

Reaction notes

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