Ethyl chloroformate → (N-1-azabicyclo[2.2.2]oct-3-yl)-8-chloro-5-ethoxy-1,2,3,4-tetrahydroquinoline-6-carboxamide

HRID 2074010ノート

反応式

HRID 2074010 の反応式
Cl[C:2]([O:4][CH2:5][CH3:6])=O.C([C:10]1[C:11]([O:21]C)=[C:12]2[C:17](=[C:18]([Cl:20])[CH:19]=1)[NH:16][CH2:15][CH2:14][CH2:13]2)(O)=O.N[CH:24]1[CH2:29][CH:28]2[CH2:30][CH2:31][N:25]1[CH2:26][CH2:27]2.C([O-])([O-])=O.[K+].[K+].C(Cl)(Cl)Cl.CC[N:44](CC)CC>C(Cl)(Cl)Cl.O>[N:25]12[CH2:31][CH2:30][CH:28]([CH2:27][CH2:26]1)[CH:29]([NH:44][C:11]([C:10]1[C:2]([O:4][CH2:5][CH3:6])=[C:12]3[C:17](=[C:18]([Cl:20])[CH:19]=1)[NH:16][CH2:15][CH2:14][CH2:13]3)=[O:21])[CH2:24]2

参加物

8

反応物 5

HCID 10928Ethyl chloroformateHCID 11430Potassium CarbonateHCID 148832326-Carboxy-8-chloro-5-methoxy-1,2,3,4-tetrahydroquinolineHCID 189269681-Azabicyclo[2.2.2]octan-2-amineHCID 18929042Triethylamine chloroform

生成物 1

HCID 19989917(N-1-azabicyclo[2.2.2]oct-3-yl)-8-chloro-5-ethoxy-1,2,3,4-tetrahydroquinoline-6-carboxamide

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6212Chloroform溶媒

反応条件

温度
-20 °C

実験手順

Ethyl chloroformate (25 ml) is added to a stirred mixture of the acid compound of step 6 above (0.7 g) in CHCl3 -Et3N (25 ml/0.8 g) chilled to -20° C. and stirring is continued for 20 min. Aminoquinuclidine (3.1 g) and a saturated aqueous K2CO3 solution (6 ml) are added to the reaction mixture. Stirring is continued for 30 minutes while slowly warning to RT. The mixture is diluted with CHCl3 and H2O, stirred for 5 minutes and the aqueous layer was separated. The organic layer is washed with H2O, dried (MgSO4) and evaporated affording a foamy solid which is chromatographed on silica and converted to the hygroscopic hydrochloride salt of the desired product, M.P. 160° C. Elemental Analysis: Calc'd C 55.96, H 6.52, N 10.88; Calc'd(as Hydrate) C 53.47, H 6.73, N 10.39; Found C 53.45, H 7.34, N 10.26. The dihydrochloride salt has the same melting point and the following elemental analysis: Calc'd C 51.13, H 6.20, N 9.94; Found C 51.41, H 6.92, N 10.15.

後処理

  1. stirringStirring
  2. waitis continued for 30 minutes
  3. customwhile slowly warning to RT
  4. stirringstirred for 5 minutes
  5. customthe aqueous layer was separated
  6. washThe organic layer is washed with H2O
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customaffording a foamy solid which
  10. customis chromatographed on silica

出典と根拠

ORDレコード
ord-3b0637889f044d4ea4555fe921f5e877
出典データセット
uspto-grants-1990_04
特許番号
US04920219

反応ノート

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