Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-10-10
1997-09-02
Richter, Johann
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
549371, 564487, C07D31906, C07D31908, C07C21302, C07C21308
Patent
active
056633726
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP95/01246 filed Apr. 5, 1995.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a process for the preparation of acetals of 2-amino-1,3-propanediol and, more particularly, it relates to a process for the preparation of 5-amino-1,3-dioxanes. The acetals of 2-amino-1,3-propanediol are advantageously used as synthetic intermediates in the preparation of the compound (S)-N,N'-bis-[2-hydroxy-1-(hydroxymethyl) ethyl]-5-[(2-hydroxy-1-oxopropyl)-amino]-2, 4,6-triiodo-1,3-benzenedicarboxamide, known with its International Nonproprietary Name Iopamidol (The Merck Index, XI Ed., page 799, No. 4943).
2. Discussion of the Background
Iopamidol was described for the first time by the Swiss Company Savac A. G. in the British patent No. 1,472,050 and is used in diagnostics as a non-ionic X-ray contrast medium.
The preparation of Iopamidol, described in said patent, comprises the condensation reaction of L-5-(2-acetoxy-propionylamino)-2, 4,6-triiodo-isophthalic acid dichloride with 2-amino-1,3-propanediol, better known as serinol, in dimethylacetamide and in the presence of a base.
Alternatively, in the same patent, a method comprising the condensation reaction of the above acid dichloride with an acetal of serinol is described; the subsequent acid hydrolysis of the resultant diacetal, carried out according to conventional techniques, allows then to obtain the desired product.
Among the possible acetals of serinol which can be used in said synthesis, for instance, 5-amino-1,3-dioxanes are cited.
Several processes for the preparation of 5-amino-1,3-dioxanes are reported in the literature.
The British patent application No. 2,081,256 (Rhone-Poulenc Industries) and the U.S. Pat. No. 3,812,186 (Eprova A. G.) describe the preparation of 5-amino-2,2-dialkyl-1,3-dioxanes by catalytic hydrogenation of the corresponding 5-nitro derivatives which, in turn, are prepared by direct cyclization of 2-nitro-1,3-propanediol with a suitable ketone, in the presence of boron trifluoride etherate.
In the U.S. Pat. No. 4,978,793 (W. R. Grace & Go.) it is described a preparation of 5-amino-2,2-dialkyl-1,3-dioxanes which comprises at first the synthesis of the corresponding 5-nitro derivatives, through a three step process starting from nitromethane and formaldehyde, and, subsequently, the reduction of the nitro group.
The processes for the preparation of 5-amino-1,3-dioxanes described in the literature evidence the remarkable drawback of using nitro derivatives, which are particularly unstable and explosive compounds, as intermediates.
Processes for the preparation of primary amines comprising the reduction of the corresponding oximes are also known in the literature.
Said reductions can be carried out by using conventional reducing agents or by means of catalytic hydrogenation [M. Hudlicky, Reduction in Organic Chemistry, Academic Press, (1984)].
Nevertheless, to the extent of our knowledge, the preparation of acetals of serinol through the reduction of the corresponding oximes has been never described in the literature.
SUMMARY OF THE INVENTION
Now we have found and it is the object of the present invention a process for the preparation of 5-amino-1,3-dioxanes of formula ##STR1## wherein
R and R.sub.1, the same or different, represent a hydrogen atom, a straight or branched C.sub.1 -C.sub.4 alkyl, an optionally substituted phenyl or, together with the carbon atom to which they are bonded, form a C.sub.5 -C.sub.6 cycloaliphatic ring, comprising the reduction of the oximes of formula ##STR2## wherein R and R.sub.1 have the above reported meanings, by catalytic hydrogenation in a suitable solvent.
The compounds of formula I can be optionally hydrolyzed to serinol according to conventional techniques.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Either the serinol or the amino acetals of formula I are useful intermediates in the preparation of Iopamidol as described, for instance, in the aforementioned British patent No. 1,472,050. With the term acetal, we intend a
REFERENCES:
patent: 2370586 (1945-04-01), Senkus
patent: 5580993 (1996-12-01), Villa et al.
Nardi Antonio
Villa Marco
Richter Johann
Stockton Laura L.
Zambon Group S.p.A.
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