Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
1999-08-27
2001-07-10
Chang, Ceila (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06258955
ABSTRACT:
BACKGROUND
The present invention relates generally to the preparation of 2-piperidineethanol compounds, and more specifically to improved processes for preparing 2-piperidineethanol compounds involving the hydrogenation of corresponding 2-pyridineethanol compounds in the presence of hydrogenation catalysts.
As further background, 2-(2-Hydroxyethyl)piperidine (also known as 2-piperidineethanol or 2-ethanolpiperidine) and related piperidine compounds are useful inter alia as intermediates to pharmacological agents and insect repellents. Various processes for preparing 2-piperidineethanol and related compounds have been described. For example, several references in the literature describe the preparation of 2-piperidineethanol via the catalytic hydrogenation of 2-pyridineethanol. Illustratively, T. S. Hamilton et al.,
J. Am. Chem. Soc
., Vol. 50, pp. 2260-2263 (1928), describes the preparation of 2-piperidineethanol hydrochloride by the catalytic reduction of 2-pyridineethanol hydrochloride in ethanol at room temperature in the presence of a platinum-oxide platinum black catalyst. A number of other references describe similar or related reductions in the presence of platinum oxide catalysts in mixed solvents containing acetic acid and either water or ethanol. See, R. R. Burtner et al.,
J. Am. Chem. Soc., Vol.
69, pp. 630-633 (1947); E. A. Steck et al.,
J. Am. Chem. Soc
., Vol. 81, pp. 6511-6514 (1959); and M. Rink et al., 60
Arch. Pharm., pp.
74-82 (1960).
Other catalyst and solvent combinations have also been tried. As examples, M. Freifelder et al.,
J. Org. Chem
., Vol. 26, pp. 3805-3808 (1961), describes a hydrogenation of 2-pyridineethanol in methanol in the presence of a ruthenium dioxide catalyst to produce 2-piperidineethanol. In later-reported work, M. Freifelder et al.,
J. Org. Chem.
, Vol. 62, pp. 284-286 (1962) describe the preparation of 2-piperidineethanol by hydrogenating the corresponding pyridine in an ethanol solvent in the presence of a rhodium on carbon catalyst. E. R. Lavagnino et al.,
J. Am. Chem. Soc., Vol.
82, pp. 2609-2613 (1960), describes a hydrogenation of 2-pyridineethanol with a palladium on carbon catalyst in water to form the corresponding piperidine.
2-piperidineethanol has also been formed by the reductive cleavage of appropriate cyclic salts of pyridine-N-oxide, as disclosed by V. Boekelheide et al,
J. Am. Chem. Soc
., Vol. 80, pp. 2217-2220 (1958).
In light of the background in this area, there has remained a need and demand for effective commercial routes to 2-piperidineethanol compounds. Such routes will desirably provide high yields and selectivities, while employing readily available starting materials and minimizing the formation of undesired byproducts that may interfere with subsequent purification or use of the 2-piperidineethanol products. The embodiments of the present invention address these needs.
SUMMARY OF THE INVENTION
It has been discovered that 2-piperidineethanol compounds can be prepared in good yields and selectivities while minimizing problematic formation of corresponding N-methylated 2-piperidineethanol byproducts, by hydrogenating corresponding 2-pyridineethanol compounds in a reaction medium including an effective amount of another amine, a high catalyst loading, and temperatures controlled to minimize byproduct formation. Accordingly, one preferred embodiment of the invention provides processes for producing 2-piperidineethanol compounds via the hydrogenation of a corresponding 2-pyridineethanol in the presence of at least about 10 mole % of another amine relative to the 2-pyridineethanol and a metal or metal oxide hydrogenation catalyst provided at a high level in the system, typically at least about 0.15 grams of catalyst (considered as the metal alone) per mole of 2-pyridineethanol compound, and desirably utilizing hydrogen pressures of at least about 500 psig and/or moderate temperatures which minimize byproduct formation, for example about 90° C. to about 120° C. Noble metal or noble metal oxide catalysts, especially ruthenium and oxides thereof (e.g. ruthenium dioxide), provide highly preferred catalysts for such processes, and the other amine is advantageously piperidine or a substituted piperidine employed as a sole or co-solvent. It has been found that the presence of the other amine in this system, combined with the use of high catalyst loadings, provides for advantageous processes with dramatically reduced formation of problematic byproducts in the reaction, particularly corresponding N-methyl-2-(2-hydroxyethyl)piperidine compounds. In more preferred processes, the other amine also serves as a solvent in the system, either alone or in combination with another solvent such as an organic solvent or water. Preferred other amines include substituted or unsubstituted piperidine, especially piperidine itself.
As to other preferences in the above-described processes, ruthenium on carbon provides a catalyst of particular advantage, and the processes are desirably conducted in the presence of hydrogen at a pressure of at least 1500 psig, typically in the range of 1500 to 5000 psig. The temperature during the hydrogenations more preferably falls within the range of about 100° C. to about 120° C., and when heterogeneous supports are used in the catalyst they are typically loaded with the metal or metal oxide to a level of about 3% to about 10% by weight. When used as the other amine, substituted piperidines can generally include any substituent that does not interfere with the hydrogenation reaction and consequent formation of the 2-piperidineethanol product. Lower alkyl-substituted piperidines are suitable for these purposes. In addition, it will be typical to include the other amine in an amount of about 10 mole % to 1000 mole % relative to the 2-pyridineethanol starting material. Any two or more of these preferences can also be combined to provide advantageous processes, and all such combinations are contemplated as being a part of the present invention.
Another preferred embodiment of the present invention provides a method for the manufacture of a 2-piperidineethanol compound, which includes conducting a series of reactions using a hydrogenation catalyst, each reaction comprising hydrogenating a corresponding 2-pyridineethanol compound in the presence of the hydrogenation catalyst and hydrogen at a pressure of at least about 500 psi. In between reactions in the series, the catalyst is contacted with an amine containing solvent for a period of time effective to condition the catalyst to improve its performance in a subsequent reaction. Such catalyst “pickling” processes have shown to unexpectedly maintain a high catalyst activity over a series of reactions.
The present invention provides processes for preparing 2-piperidineethanol compounds by the catalytic hydrogenation of corresponding 2-pyridineethanol compounds, with high yield and selectivity, and minimal formation of problematic N-methyl-2-(2-hydroxyethyl)piperidine byproducts. The preferred processes can be conducted using readily available equipment and starting materials, and under conditions attractive for commercial implementation. These and other features and advantages of the present invention will be apparent from the descriptions herein.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
For the purpose of promoting an understanding of the principles of the invention, reference will now be made to certain preferred embodiments thereof and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended, such alterations, further modifications and applications of the principles of the invention as described herein being contemplated as would normally occur to one skilled in the art to which the invention relates.
As indicated above, the present invention provides improved processes for preparing 2-piperidineethanol compounds. Preferred processes of the invention involve the hydrogenation of a corresponding 2-pyridineethanol compound in the presence of another
Chang Ceila
Reilly Industries Inc.
Woodard Emhardt Naughton Moriarty & McNett
LandOfFree
Process for preparing 2-piperidineethanol compounds does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for preparing 2-piperidineethanol compounds, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for preparing 2-piperidineethanol compounds will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2510072