合成路线1

Sabcomeline can be obtained by several related ways: 1) The reaction of N-methoxyquinuclidine-3-carboxamide (I) with triphenylphosphine in refluxing CCl4 or with PCl5 in nitromethane gives N-methoxyquinuclidin-3-ylcarboxyimidoyl chloride (II), which by reaction with NaCN in hot DMSO is converted into 2-(methoxyimino)-2-(3-quinuclidinyl)acetonitrile (III). Finally, this compound is submitted to optical resolution with (R)-(-)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate [(R)-(-)-BNHP], or with 2,3:4,6-di-O-isopropylidene-2-oxo-L-gulonic acid [L-DIOG]. 2) The condensation of diethyl cyanomethylphosphonate (IV) with 3-quinuclidinone (V) by means of KOH in water gives 2-(quinuclidin-3-ylidene)acetonitrile (VI), which is hydrogenated with H2 over Pd/C in ethyl acetate to yield 2-(quinuclidin-3-yl)acetonitrile (VII). The nitrosation of (VII) with isoamyl nitrile and potassium tert-butoxide in THF affords 2-(hydroxyimino)-2-(3-quinuclidinyl)acetonitrile (VIII), which is methylated with methyl p-toluenesulfonate and potassium tert-butoxide in DMSO to give 2-(methoxyimino)-2-(3-quinuclidinyl)acetonitrile (III), already obtained. 3) The condensation of 3-quinuclidinone (V) with cyanacetic acid (IX) by means of NaOH in water gives 2-(quinuclidin-3-ylidene)cyanacetic acid (X), which is hydrogenated with H2 over Pd/C in water to yield 2-(3-quinuclidinyl)cyanacetic acid (XI). Finally, this compound is nitrosated with NaNO2/HCl to afford 2-(hydroxyimino)-2-(3-quinuclidinyl)acetonitrile (VIII), already obtained.