Dicyclohexylcarbodiimide → 4-Amino-N-(1-azabicyclo[2.2.2]octan-3-yl)-5-chloro-2-(cyclopropylmethoxy)benzene-1-carboximidic acid

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Reaction Steps

To a solution of 2-cyclopropylmethoxy-4-amino-5-chlorobenzoic acid (3.2 g; 0.0134 moles) in pyridine (15 ml), a solution of 3-aminoquinuclidine dihydrochloride (2.5 g; 0.0125 moles) and sodium hydroxide (0.5 g; 0.0125 moles) in water (15 ml) was added. To the resulting solution, N,N'-dicyclohexyl-carbodiimide (3.1 g; 0.0146 moles) was added and the mixture stirred at room temperature for 20 hours. An additional amount of N,N'-dicyclohexyl-carbodiimide (3.1 g; 0.0146 moles) was added and the mixture stirred for a further 24 hours. The insoluble solid was filtered off, washed with water and the solvent removed in vacuo at a temperature between 30° and 45° C. The solid residue was taken up in water, made alkaline with sodium hydroxide and a solid precipitated which was filtered off and dried to give N-(1-azabicyclo[2.2.2]oct-3-yl)-2-cyclopropylmethoxy-4-amino-5-chlorobenzamide (4.1 g) M.p. 183°-185° C. after recrystallisation from acetonitrile.

Provenance & Evidence