Ethyl chloroformate → (N-1-azabicyclo[2.2.2]oct-3-yl)-7-chloro-4-methoxy-2,3-dihydroindole-5-carboxamide

HRID 2074004Notes

Reaction equation

HRID 2074004 reaction equation
ClC(OCC)=O.C([N:10]1[C:18]2[C:13](=[C:14]([O:23][CH3:24])[C:15]([C:20]([OH:22])=O)=[CH:16][C:17]=2[Cl:19])[CH2:12][CH2:11]1)(=O)C.N[CH:26]1[CH2:31][CH:30]2[CH2:32][CH2:33][N:27]1[CH2:28][CH2:29]2.C([O-])([O-])=O.[K+].[K+].C1(N)C(F)=C(F)C(F)=C([NH2:49])C=1F.Cl.Cl>C(Cl)(Cl)Cl.CCN(CC)CC.C(Cl)(Cl)Cl.O.Cl.CO>[N:27]12[CH2:33][CH2:32][CH:30]([CH2:29][CH2:28]1)[CH:31]([NH:49][C:20]([C:15]1[C:14]([O:23][CH3:24])=[C:13]3[C:18](=[C:17]([Cl:19])[CH:16]=1)[NH:10][CH2:11][CH2:12]3)=[O:22])[CH2:26]2

Participants

10

Reactant 5

HCID 10928Ethyl chloroformateHCID 11430Potassium CarbonateHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 148832261-Acetyl-5-carboxy-7-chloro-4-methoxy-1,2-dihydroindoleHCID 189269681-Azabicyclo[2.2.2]octan-2-amine

Product 1

HCID 14883227(N-1-azabicyclo[2.2.2]oct-3-yl)-7-chloro-4-methoxy-2,3-dihydroindole-5-carboxamide

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 18929042Triethylamine chloroformSolventHCID 21893726Hydrochloride methanolSolvent

Conditions

Temperature
-20 °C

Procedure

Ethyl chloroformate (25 ml) is added to a stirred mixture of the acid compound of step 10 above (0.7 g) in CHCl3 -Et3N (25 ml/0.7 g) chilled to -20° C. and stirring is continued for one hour. Aminoquinuclidine (2.8 g) and a saturated aqueous K2CO3 solution (7 ml) are added to the reaction mixture. Stirring is continued for 2 hours 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 converted to the dihydrochloride salt by dissolving in HCl-MeOH and evaporating the solvent. The desired product in the form of the dihydrochloride salt is a hygroscopic material is determined to be the correct material by NMR. M.P.=151°-153° C. Elemental Analysis: Calc'd C: 49.95, H 5.92, N 10.28; Found C: 50.58, H 6.20, N 9.98.

Workup

  1. stirringStirring
  2. waitis continued for 2 hours
  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. customevaporating the solvent

Sources & evidence

ORD record
ord-86ae02f9e1a64f8b97c89fe0ae549647
Source dataset
uspto-grants-1990_04
Patent number
US04920219

Reaction notes

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