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

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Reaction Conditions

Reaction Steps

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.

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