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# 1 United States Patent Office 

## DERIVATIVES OF IBOGAMINE, IBOGAINE AND IBOGALINE LACTAMS Wataru Nagata, Nishinomiya, 

and Shoichi Hirai, lbaraki, Japan, assignors to Shionogi & Co., Ltd., Osaka, Japan No Drawing. 

Original application May 28, 1968, Ser. No. 732,520, now Patent No. 3,663,940. Divided and this application Oct. 14, 1970, Ser. No. 80,806 Claims priority, application Japan, June 3, 1967, 42/35,647; Feb. 7, 1968, 43/7,620 Int. Cl. C07d 43/38 U.S. Cl. 260-239.3 P 10 Claims 

Lactams of ibogamine, ibogaine and ibogaline com› pounds, such as 4-desethyl-18-p-toluensulfonyloxyibog› amine lactam, are provided, which are useful as inter› mediates in preparing isoquinuclidine alkaloids useful as medicaments. 

This application is a drvision of Ser. No. 732,520 filed May 28, 1968, now U.S. Pat. No. 3,663,940. 

The present invention relates to a process for the prep› aration of a series of known and useful alkaloids of isoquinuclidine-type, particularly the components of the iboga plants such as ibogamine, ibogaine, ibogaline, or the homologues, which is characterized by totally syn› thesizing the said compounds briefly and stereospecifically utilizing the peculiar and advantageous reactivity of novel and unusual cyclic compounds, i.e. 1-azatricyclo,[3.2. 1.02- 7 ]octanes and the homologues (I) which have been 

## ABSTRACT OF THE DISCLOSURE 

## 1 

3,716,528 

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prepared by the present inventors. Most advantageously the present invention provides an improved method for the preparation of these a1kaloids useful as medicaments. 

The process of the present invention comprises inter- acting a starting aziridine compound (I) with an indole› acetic acid.anhydride (II) followed by hydrolysis to give an isoquinuclidine (UI) [the 1st step], oxidizing the lat› ter to give a compound (IV) [the 2nd step], interacting the latter with an organic acid to give a compound (V) [the 3rd step], subjecting to solvolysis the latter to give a compound (VI) [the 4th step], reducing the latter with a metal hydride to give a vinyl amine (VII) [the 5th step], catalytically hydrogenating the latter to give a compound (VIII) [the 6th step], and then treating ilie latter with a metal hydride to give the final compound (.IX) [the 7th step], or, alternatively in the 3rd step in the above-described process, interacting the compound (IV) with an acid in the presence of a lower alcohol directly to give the compound (VI) corresponding to the product of the 4th step [the 3rd step], or in the 4th step, reducing the compound (V) with an aluminum hydride represented by the general formula AIH•Z•Z’ (wherein Z and Z’ are the same or different and each is a hydrogen atom, a lower alkyl group, e.g. methyl, ethyl, propyl, i-propyl, butyl, i-butyl, a lower alkoxy group, e.g. me› thoxy, ethoxy, propoxy, i-propoxy, butoxy, i-butoxy, t-butoxy, or a halogen atom, e.g. chlorine, bromine, iodine) directly to give the final compound (IX) [4’th step] and/or the intermediate (X), being catalytically hydrogenated to the final compound (IX) [ 4"th step]. The reaction sequence is represented by the following reaction scheme. 

Patented Feb. 13, 1973 

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