Adamantanone → 2-Adamantanone oxime

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Reaction Steps

To 30 g of 2-adamantanone (Aldrich Chem. Co.) in 100 mL of methanol was added 50 g of hydroxylamine hydrochloride and 92 g of sodium acetate trihydrate and the mixture was refluxed for 2 hours. The mixture was concentrated in vacuo, the residue was distributed between 250 of dichloromethane and 50 mL of water. The organic layer was separated, dried with magnesium sulfate and concentrated in vacuo to give 30 g of crude 2-adamantanone oxime. This was dissolved in 100 mL of chloroform and 135 g of PPE (polyphosphate ester, prepared by refluxing phosphorus pentoxide with diethyl ether in chloroform, as described by G. Schramm, H. Groetsch, and W. Pollmann, Angew. Chem., Internat. Ed., 1,1 (1962)) was added carefully. When the exothermic reaction ceased, the mixture was refluxed for 5 minutes. Then it was cool in ice, diluted with 500 mL of water and stirred overnight. The organic layer was separated, dried with magnesium sulfate and concentrated in vacuo to give 16.6 g of the crude lactam product. This was dissolved in 250 of chloroform and 11 mL of phosphorus oxychloride was added dropwise in 30 minutes. To this was then added a solution of 15 g of 4,6-dichloroanthranilic acid and 4 of triethylamine in 150 mL of chloroform in 25 minute at room temperature. Then the mixture was refluxed for 16 hours. Column chromatography using 50:1 to 25:1 chloroform:methanol on silica gel provided 16 g of 1,3-dichloro-7,8,9,10,11,12-hexahydro-6,10:8,12-dimethanoazonino[2,1-b]quinazolin-14(6H)-one as white coarse crystals. This was then reduced with zinc and hydrochloric acid to the 1,3-dichloro-6,7,8,9,10,11,12,14-octahydro-6,10:8,12-dimethanoazonino[2,1-b]quinazoline by the same procedure as described in Example 2 to give after treatment with 1 equivalent of HCl and recrystallization from absolute alcohol/ethyl acetate 1,3-dichloro-6,7,8,9,10,11,12,14-octahydro-6,10:8,12-dimethanoazonino[2,1-b]quinazoline monohydrochloride as white crystalline solid, with m.p. 310° C. (dec.).

Provenance & Evidence