Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2003-01-06
2004-11-09
Chang, Celia (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C546S216000, C546S221000, C514S321000
Reexamination Certificate
active
06815548
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a piperidine derivative and a process for preparing the same More particularly, the present invention relates to a piperidine derivative useful as an intermediate for pharmaceuticals such as paroxetine and the like which are useful, for example, as an antidepressant.
2. Discussion of the Related Art
In general, paroxetine useful as an antidepressant is prepared by the processes described, for example, in Japanese Unexamined Patent Publication No. 7-138228 and Japanese Examined Patent Publication No. 59-46216.
However, these processes have the drawback that, upon deprotection of N-methyl group, complicated procedures such as hydrolysis after the transformation of N-methyl group to carbamate group are required.
In addition, there is disclosed a process for preparing paroxetine using an amidomalonic acid ester derivative as a starting material in, for example, Japanese Unexamined Patent Publication No. 7-138228. However, the amidomalonic acid ester derivative is not in general commercially available. Therefore, there necessitates troublesome procedures such that the amidomalonic acid ester derivative should be previously prepared before using.
An object of the present invention is to provide a compound useful as an intermediate for preparing paroxetine and a process for simply and industrially preparing the compound.
These and other objects of the present invention will be apparent from the following description.
SUMMARY OF THE INVENTION
Specifically, the present invention is concerned with the following:
(1) A piperidine derivative represented by the general formula (I):
wherein R
1
is hydrogen atom, benzyloxycarbonyl group or tert-butoxycarbonyl group; R
2
is hydroxymethyl group, an alkylsulfonyloxymethyl group having an alkyl moiety of 1 to 2 carbon atoms, phenylsulfonyloxymethyl group which may have methyl group at the 4-position, (3,4-methylenedioxyphenyl)oxymethyl group, carboxyl group or —CO
2
R
7
group in which R
7
is an alkyl group having 1 to 5 carbon atoms, and Z is methylene group or carbonyl group, with proviso that,
(A) when R
1
is benzyloxycarbonyl group or tert-butoxycarbonyl group, then R
2
is hydroxymethyl group, an alkylsulfonyloxymethyl group having an alkyl moiety of 1 to 2 carbon atoms, phenylsulfonyloxymethyl group which may have methyl group at the 4-position or (3,4-methylenedioxyphenyl)oxymethyl group, and Z is methylene group; or
(B) when R
1
is hydrogen atom and Z is carbonyl group, then R
2
is carboxyl group or —CO
2
R
7
group (R
7
is as defined above); or
(C) when R
1
is hydrogen atom and Z is methylene group, then R
2
is hydroxymethyl group;
(2) The piperidine derivative described in the above item (1), wherein the piperidine derivative is at least one member selected from (3S,4R)-trans-1-benzyloxycarbonyl-4-(4-fluorophenyl)-3-[(3,4-methylenedioxyphenyl)-oxymethyl]piperidine, (3SR,4RS)-trans-1-benzyloxy-4-(4-fluorophenyl)-3-[(3,4-methylenedioxyphenyl)oxymethyl]-piperidine, (3S,4R)-trans-1-tert-butoxycarbonyl-4-(4-fluorophenyl)-3-[(3,4-methylenedioxyphenyl)oxymethyl]-piperidine, (3SR,4RS)-trans-1-tert-butoxycarbonyl-4-(4-fluorophenyl)-3-[(3,4-methylenedioxyphenyl)oxymethyl]-piperidine, (3S,4R)-trans-1-benzyloxycarbonyl-4-(4-fluorophenyl)-3-methylsulfonyloxymethylpiperidine, (3SR,4RS)-trans-1-benzyloxycarbonyl-4-(4-fluorophenyl)-3-methylsulfonyloxymethylpiperidine, (3S,4R)-trans-1-tert-butoxycarbonyl-4-(4-fluorophenyl)-3-methylsulfonyloxymethylpiperidine, (3SR,4RS)-trans-1-tert-butoxycarbonyl-4-(4-fluorophenyl)-3-methylsulfonyloxymethylpiperidine, (3S,4R)-trans-1-benzyloxycarbonyl-4-(4-fluorophenyl)-3-ethylsulfonyloxymethylpiperidine, (3SR,4RS)-trans-1-benzyloxycarbonyl-4-(4-fluorophenyl)-3-ethylsulfonyloxymethylpiperidine, (3S,4R)-trans-1-tert-butoxycarbonyl-4-(4-fluorophenyl)-3-ethylsulfonyloxymethylpiperidine, (3SR,4RS)-trans-1-tert-butoxycarbonyl-4-(4-fluorophenyl)-3-ethylsulfonyloxymethylpiperidine, (3S,4R)-trans-1-benzyloxycarbonyl-4-(4-fluorophenyl)-3-phenylsulfonyloxymethylpiperidine, (3SR,4RS)-trans-1-benzyloxycarbonyl-4-(4-fluorophenyl)-3-phenylsulfonyloxymethylpiperidine, (3S,4R)-trans-1-tert-butoxycarbonyl-4-(4-fluorophenyl)-3-phenylsulfonyloxymethylpiperidine, (3SR,4RS)-trans-1-tert-butoxycarbonyl-4-(4-fluorophenyl)-3-phenylsulfonyloxymethylpiperidine, (3S,4R)-trans-1-benzyloxycarbonyl-4-(4-fluorophenyl)-3-(4-methylphenyl)sulfonyloxymethylpiperidine, (3SR,4RS)-trans-1-benzyloxycarbonyl-4-(4-fluorophenyl)-3-(4-methylphenyl)sulfonyloxymethylpiperidine, (3S,4R)-trans-1-tert-butoxycarbonyl-4-(4-fluorophenyl)-3-(4-methylphenyl)sulfonyloxymethylpiperidine, (3SR,4RS)-trans-1-tert-butoxycarbonyl-4-(4-fluorophenyl)-3-(4-methylphenyl)sulfonyloxymethylpiperidine, (3S,4R)-trans-1-benzyloxycarbonyl-4-(4-fluorophenyl)-3-hydroxymethylpiperidine, (3SR,4RS)-trans-1-benzyloxycarbonyl-4-(4-fluorophenyl)-3-hydroxymethylpiperidine, (3S,4R)-trans-1-tert-butoxycarbonyl-4-(4-fluorophenyl) -3-hydroxymethylpiperidine, (3SR,4RS)-trans-1-tert-butoxycarbonyl-4-(4-fluorophenyl)-3-hydroxymethylpiperidine, (3S,4R)-trans-4-(4-fluorophenyl)-3-hydroxymethylpiperidine, (4R,5S)-trans-5-carboxy-4-(4-fluorophenyl)piperidin-2-one, and (4RS,5SR)-trans-5-carboxy-4-(4-fluorophenyl)piperidin-2-one;
(3) The piperidine derivative described in the above item (1), wherein R
1
is tert-butoxycarbonyl group or benzyloxycarbonyl group, R
2
is a group represented by the formula:
and Z is methylene group in the general formula (I);
(4) A method for preparing a piperidine derivative represented by the general formula (VII);
wherein R
3
is benzyl group or tert-butyl group, comprising the steps of:
reacting (3S,4R)-trans-4-(4-fluorophenyl)-3-hydroxymethylpiperidine represented by the formula (II):
with a protecting reagent represented by the general formula (III):
wherein R
3
is as defined above; and Y is a chlorine atom or tert-butoxycarbonyloxy group, with proviso that
(A) when R
3
is benzyl group, then Y is a chlorine atom,
(B) when R
3
is tert-butyl group, then Y is tert-butoxycarbonyloxy group,
to give a carbamate compound represented by the general formula (IV):
wherein R
3
is as defined above;
reacting the carbamate compound with a sulfonic acid chloride represented by the general formula (V):
wherein R
4
is an alkyl group having 1 to 2 carbon atoms or a phenyl group which may have methyl group at the 4-position, to give a sulfonic acid ester represented by the general formula (VI):
wherein R
3
and R
4
are as defined above;
reacting the sulfonic acid ester with 3,4-methylenedioxyphenol under basic conditions;
(5) A method for preparing (3S,4R)-trans-4-(4-fluorophenyl)-3-hydroxymethylpiperidine represented by the formula (II):
comprising the steps of:
optically resolving (4RS,5SR)-trans-5-carboxy-4-(4-fluorophenyl)piperidin-2-one, to give (4R,5S)-trans-5-carboxy-4-(4-fluorophenyl)piperidin-2-one represented by the formula (VIII):
and reducing the (4R,5S)-trans-5-carboxy-4-(4-fluorophenyl)piperidine with a metal hydride compound;
(6) A method for preparing (3S,4R)-trans-4-(4-fluorophenyl)-3-hydroxymethylpiperidine represented by the formula (II):
comprising the step of optically resolving (3SR,4RS)-trans-4-(4-fluorophenyl)-3-hydroxymethylpiperidine;
(7) A method for preparing (3S,4R)-trans-4-(4-fluorophenyl)-3-hydroxymethylpiperidine represented by the formula (II):
comprising the steps of:
transforming (±)-cis,trans-4-(4-fluorophenyl)-5-alkyloxycarbonylpiperidin-2-one represented by the general formula (IX):
wherein R
5
is an alkyl group having 1 to 4 carbon atoms; in the presence of a base, to give (4RS,5SR)-trans-4-(4-fluorophenyl)-5-alkyloxycarbonylpiperidin-2-one;
reducing the (4RS,5SR)-trans-4-(4-fluorophenyl)-5-alkoxycarbonylpiperidin-2-one with a metal hydride compound, to give (3SR,4RS)-trans-4-(4-fluorophenyl)-3-hydroxymethylpiperidine; and
optically resolving the (3SR,4RS)-trans-4-(4-fluorophenyl)-3-hydroxymethylpiperidine;
(8) A method for preparing (3S,4R)-trans-4-(4-fluorophenyl)-3-[(3,4-methylenedioxyp
Igi Masami
Ishibashi Taro
Itaya Nobushige
Katsura Tadashi
Kawada Yoshihiro
Chang Celia
Sumika Fine Chemicals Co., Ltd.
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