1-Azabicyclo -3-octanol

A solution of 50 g of 1 -azabicyclo [2.2.2] -3-octanone hydrochloride in 200 cc of water was hydrogenated at room temperature and 50 atm pressure with 1 g of platinum oxide as catalyst. After the calculated amount of hydrogen had been absorbed, the mixture was filtered and concentrated in vacuo to dryness. The residual product was recrystallized from a mixture of methanol and acetone and formed prisms melting above 300°C. It was identified as 1 -ezabicy-clo[2.2.2] -3-octanol hydrochloride. 

A solution of 50 g of 1 -azabicyclo[2.2.2] -3-octanol hydrochloride in 30 cc water was made alkaline with 30 g of potassium hydroxide. After the alkali was dissolved 35 g of granular potassium carbonate were added. The free basic alcohol was then extracted from the viscous mixture by shaking with four portions of boiling benzene (300 cc in each portion). The benzene extracts were decanted and filtered over anhydrous sodium sulfate, to remove any suspended alkali. The combined benzene solutions were concentrated in vacuo. The residue was recrystallized from benzene and identified as 1 -azabicyclo[2.2.2] -3-octanol, MP 221°-223°C. The product can also be purified by recrystallization from acetone, or by sublimation in vacuo (120°C/20 mm Hg). The alcohol was reacted with acetic anhydride to give the product ace-clidine. 

The hydrogeh atom bound to the amide nitrogen in 15 is rather acidic and it can be easily removed as a proton in the presence of some competent base. Naturally, such an event would afford a delocalized anion, a nucleophilic species, which could attack the proximal epoxide at position 16 in an intramolecular fashion to give the desired azabicyclo[3.2.1]octanol framework. In the event, when a solution of 15 in benzene is treated with sodium hydride at 100 °C, the processes just outlined do in fact take place and intermediate 14 is obtained after hydrolytic cleavage of the trifluoroacetyl group with potassium hydroxide. The formation of azabi-cyclo[3.2.1]octanol 14 in an overall yield of 43% from enone 16 underscores the efficiency of Overman s route to this heavily functionalized bicycle. 

To find the structure-activity relationships in this series esters of both non-substituted 3-hydroxyquinuclidine and 3-hydroxyquinuclidines having various substituents in the 3-, 6- and other positions have been synthesized. Esters of homologous aminoalcohols 3-hydroxymethyl- and 3-(j8-hydroxyethyl)-qui-nuchdines, esters of isomeric and homologous 1-azabicycloalkanols - 1-aza-bicyclo(3,2,l)-octanol-6 and l-azabicyclo(3,3,2)-nonanole-4 and also esters containing the opened 3-hydroxy-quinuclidine structure, e.g. AT-alkyl-3-hy-... 

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