Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1998-03-26
2000-04-25
Kight, John
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
546245, C07D21106, C07D21160
Patent
active
060545860
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELDS
The present invention relates to a process for preparing 4-methylenepiperidine which is an intermediate for the synthesis of a compound having a formula (VIII): ##STR5## (a compound described in Example 1 in the published International Application No. WO 94/26734(1994)) known to be useful as a fungicide.
BACKGROUND ART
As a process for synthesizing 4-methylenepiperidine, there have been known the method wherein an aqueous solution of 4-bromoquinuclidine is heated (P. Brenneisen et al., Helv. Chim. Acta, 48(1), 146-156(1965)) and the method wherein N-benzyl-4-piperidone is reacted with a Wittig reagent and then debenzylation is carried out to obtain 4-methylenepiperidine (M. Mimura et al., Chem. Pharm. Bull., 41(11), 1971-1986(1993)). However, by either of these methods, it is difficult to manufacture a large amount of 4-methylenepiperidine at low cost because of the difficulty of obtaining the starting material or the use of an expensive reagent such as the Wittig reagent.
The object of the present invention is to provide a process for preparing 4-methylenepiperidine efficiently in short process from a cheap starting material which is obtainable at large amount.
DISCLOSURE OF THE INVENTION
As the result of the continuous effort and detailed investigation of the present inventors to achieve the above-mentioned object, they have found a process for preparing 4-methylenepiperidine at low cost wherein a starting material is an isonipecotate which is easily obtainable at low price.
The present invention relates to ##STR6## wherein R.sup.2 is benzoyl group or acetyl group, which comprises reacting a halide having a formula (V): ##STR7## wherein X is chlorine atom or bromine atom and R.sup.2 is the same as defined above, with a dehydrohalogenating agent in an organic solvent, ##STR8## wherein R.sup.2 is benzoyl group or acetyl group, which comprises reducing an ester having a formula (III): ##STR9## wherein R.sup.1 is methyl group or ethyl group and R2 is the same as defined above, with sodium borohydride or lithium borohydride in an organic solvent containing methanol, ##STR10## wherein X is chlorine atom or bromine atom and R.sup.2 is benzoyl group or acetyl group, which comprises reacting an alcohol having a formula (IV): ##STR11## wherein R.sup.2 is the same as defined above, with a halogenating agent without any solvent or in an organic solvent in the presence or the absence of a base, ##STR12## wherein R.sup.2 is benzoyl group or acetyl group, which comprises reducing an ester having a formula (III): ##STR13## wherein R.sup.1 is methyl group or ethyl group and R.sup.2 is the same as defined above, with sodium borohydride or lithium borohydride in an organic solvent containing methanol, reacting a resulting alcohol having a formula (IV): ##STR14## wherein R.sup.2 is the same as defined above, with a halogenating agent without any solvent or in an organic solvent in the presence or the absence of a base and reacting a resulting halide having a formula (V): ##STR15## wherein X is chlorine atom or bromine atom and R.sup.2 is the same as defined above, with a dehydrohalogenating agent in an organic solvent, ##STR16## wherein R.sup.1 is methyl group or ethyl group and R.sup.2 is benzoyl group or acetyl group, which comprises reacting an isonipecotate having a formula (I): ##STR17## wherein R.sup.1 is the same as defined above, with an acylating agent having a formula (II): R.sup.2 X or a formula (II'): (R.sup.2).sub.2 O wherein R.sup.2 is the same as defined above and X is chlorine atom or bromine atom, in the presence or the absence of a base, ##STR18## which comprises hydrolyzing a methylene compound having a formula (VI): ##STR19## wherein R.sup.2 is benzoyl group or acetyl group, with a strong alkaline in water or an organic solvent containing water, and ##STR20## which comprises reacting an isonipecotiate having a formula (I): ##STR21## wherein R.sup.1 is methyl group or ethyl group, with an acylating agent having a formula (II): R.sup.2 X or a formula (II'): (R.sup.2).sub.2 O wherein
REFERENCES:
patent: 4243807 (1981-01-01), Friebe et al.
patent: 5298503 (1994-03-01), Peglion et al.
patent: 5620994 (1997-04-01), Naito et al.
Bingwei V. Yang et al. Mild and Selective Debenzylation of Tertiary Amines Using .alpha.-Chloroethyl Chloroformate:, Synlett, 1993, vol. 3, pp. 195-196.
International Search Report.
P. Brenneisen et al., Helvetica Chimica Acta, 48(1), 146-156 (1965).
Derwent Abstract WPI No. 92-173201/199221 of JP 4-112868.
Covington Raymond
Kaken Pharmaceutical Co. Ltd.
Kight John
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