Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2000-08-04
2002-06-11
Geist, Gary (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C564S303000, C560S070000, C560S070000
Reexamination Certificate
active
06403832
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a method for producing optically active 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid by resolving racemic 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid with an optically active amine compound, novel optically active amine compound therefor and its production process.
2. Description of Related Art
Optically active 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid is a useful intermediate compound of pharmaceuticals for urinary incontinence as described in WO97/14672 and also of agrochemicals.
There have been reported a method in which racemic 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid is resolved with optically active &agr;-methylbenzylamine (J. Med. Chem., 1996, 39, 4592-4601) and a method in which racemic 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid is optically resolved with brucine and followed by repeated recrystallizations (J. Chem. Soc., 1951, 2329-2332).
SUMMARY OF THE INVENTION
An object of the present invention is to provide a diastereomer salt comprising a specific optically active amine and optically active 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid, which is suitable for producing optically active 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid having good optical purity,
another object of the invention is to provide a process for producing optically active 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid in industrially advantageous manner,
further objects of the invention are to provide
novel optically active amine compounds suitable for optical resolution,
intermediate compounds for producing the optically active amines, and
processes for producing the intermediate compounds.
The present invention provides:
1. A diastereomer salt of formula (1):
wherein each asymmetric carbon atom denoted by the symbol * is independently in S configuration or R configuration,
R
1
represents a lower alkyl group which may be substituted with a hydroxy group, or an optionally substituted aryl group,
R
2
represents a lower alkyl group which may be substituted with a hydroxy group, or an optionally substituted aralkyl group, and
R
3
represents a lower alkyl group which may be substituted with a hydroxy group, a hydrogen atom, a cyclohexyl group, or an optionally substituted aralkyl group,
provided that R
1
and R
2
are not the same, and when R
1
is a phenyl group and R
2
is a methyl group, R
3
is not a hydrogen atom;
2. A method for producing a diastereomer salt of formula (1) as defined above, which comprises contacting racemic 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid of formula (2):
with an optically active amine of formula (3):
wherein the symbol *, R
1
, R
2
, and R
3
respectively represent the same as defined above to form diastereomer salt(s), and separating said diastereomer salt of formula (1);
3. A method for producing an optically active 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid of formula (2′):
wherein an asymmetric carbon atom denoted by the symbol * is in S configuration or R configuration,
which comprises treating the salt of formula (1) as defined above, with an acid, or a base and an acid;
4. An optically active amine compound of formula (4):
wherein an asymmetric carbon atom denoted by the symbol * is in S configuration or R configuration,
R
11
represents an aryl group which may be substituted with at least one group selected from a, C1-C4 alkyl group, a C1-C4 alkoxy group, a nitro group and a halogen atom,
R
21
represents a C1-C4 alkyl group, or an aralkyl group which may be substituted, and
R
31
is a 3-benzyloxyphenyl group or a 4-benzyloxyphenyl group, or a salt thereof;
5. A method for producing an optically active amine compound of formula (4) as defined above, or a salt thereof, which comprises:
reducing an imine compound of formula (7);
wherein the symbol *, R
11
, R
21
and R
31
respectively have the same meaning as defined above, to a reduction reaction;
6. An imine compound of formula (7) as defined above,
7. A method for producing an imine compound of formula (7) as defined above, which comprises:
reacting an optically active amine of formula (5):
wherein the symbol * denotes an asymmetric carbon atom,
R
11
and R
21
respectively represent the same as defined above, with a benzyloxybenzaldehyde of formula (6):
R
31
—CHO (6)
wherein R
31
represents a 3-benzyloxyphenyl group or a 4-benzyloxyphenyl group;
8. An optically active amine compound of formula (8):
wherein X
1
represents a halogen atom, or a lower alkyl group,
X
2
to X
5
are the same or different and independently represent a hydrogen atom, a halogen atom, a nitro group or a lower alkyl group,
R
22
represents a lower alkyl group, and
R
32
represents an aryl group substituted with at least one group selected from a lower alkyl group, a lower alkoxy group, an aryl group, and an aryloxy group;
9. A method for producing an optically active amine compound of formula (8) as defined above, which comprises:
subjecting an imine compound of formula (11):
wherein X
1
to X
5
, R
22
and R
32
are the same as defined above, to a reduction reaction.
10. An imine compound of formula (11) as defined above; and
11. A method for producing an imine compound of formula (11) as defined above, which comprises:
reacting an optically active amine compound of formula (9):
wherein X
1
to X
5
and R
22
are the same as defined above, with an aldehyde of formula (10):
R
32
—CHO (10)
wherein R
32
represents the same as defined above.
DETAILED DESCRIPTION OF THE INVENTION
First a descritpion will be made to the diastereomer salt of formula (1).
Racemic 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid (2) can be prepared by a known method as disclosed in J. Chem. Soc., 1951, 2329-2332 or the like.
The substituent groups R
1
, R
2
, and R
3
of the optically active amine compound of formula (3) will be explained below.
Examples of the lower alkyl group which may be substituted with a hydroxy group, in R
1
, R
2
, and R
3
include a C1-C4 alkyl group which may be substituted with a hydroxy group.
Specific examples thereof include a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a t-butyl group, a sec-butyl group, an i-butyl group, a hydroxymethyl group, a 2-hydroxyethyl group, a 2-hydroxypropyl group, a 2-hydroxy-2-methylpropyl group and the like.
In R
3
, the hydroxy group which may be present on the alkyl moiety of the alkyl group which may be substituted with a hydroxy group is not on a carbon atom which is bound with the nitrogen atom.
Examples of the optionally substituted aryl group, in R
1
include a phenyl group, a naphthyl group and the like, all of which may be substituted with at least one group selected from a C1-C4 alkyl group, a C1-C4 alkoxy group, a nitro group and a halogen atom.
The C1-C4 alkyl group on the aromatic ring of the aryl groups includes a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a t-butyl group, a sec-butyl group and an i-butyl group.
The C1-C4 alkoxy group on the aromatic ring of the aryl groups includes a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a t-butoxy group and the like.
Examples of the halogen atom on the aromatic ring include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
Specific examples of the optionally substituted aryl group include a phenyl group, a naphthyl group, a 4-methylphenyl group,
a 4-ethylphenyl group, a 4-propylphenyl group, a 4-isopropylphenyl group,
a 4-t-butylphenyl group, a 2,5-dimethylphenyl group,
a 2,4,6-trimethylphenyl group, a 2-fluorophenyl group,
a 3-fluorophenyl group, a 4-fluorophenyl group, a 2-chlorophenyl group,
a 3-chlorophenyl group, a 4-chlorophenyl group, a 2,4-dichlorophenyl group,
a 2,3-dichlorophenyl group, a 4-bromophenyl group,
a 2-methoxyphenyl group, a 4-methoxyphenyl group,
a 2-ethoxyphenyl group, a 2-propoxyphenyl group,
a 3,4-dimethoxyphenyl group, a 2-methoxy-5-fluorophenyl group and the like.
The optionally subst
Higashii Takayuki
Kurimoto Isao
Oikawa Miyuki
Ushio Hideki
Birch & Stewart Kolasch & Birch, LLP
Geist Gary
Reyes Hector M
Sumitomo Chemical Company Limited
LandOfFree
Process for producing optically active... 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 producing optically active..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for producing optically active... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2941320