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

HRID 466609ノート

反応式

HRID 466609 の反応式
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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒2 回

反応条件

温度
85 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-4118b8d934a54612bdaa903b7e808dc3
出典データセット
uspto-grants-1992_10
特許番号
US05157038

反応ノート

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