Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...
Reexamination Certificate
2002-02-19
2004-10-12
Bernhardt, Emily (Department: 1624)
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitrogen attached directly or indirectly to the purine ring...
C544S396000
Reexamination Certificate
active
06803465
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a method for producing 1-[(substituted phenyl)phenylmethyl]piperazine, which is useful as intermediates for pharmaceuticals and the like, more particularly, for example, to an intermediate for the production of antiallergic pharmaceuticals disclosed in JP-A-7-2816.
BACKGROUND OF THE INVENTION
An optical resolution method of an optically active 1-[(substituted phenyl)phenylmethyl]piperazine is disclosed in GB 2225321, which method comprises reacting racemic 1-[(4-chlorophenyl)phenylmethyl]piperazine with an optically active tartaric acid to form a salt.
JP-A-7-2816 discloses a method comprising the steps of performing optical resolution by allowing racemic (4-chlorophenyl)phenylmethylamine to react with optically active tartaric acid to form a salt, reacting the salt with N,N-bis(2-chloroethyl)-4-methylbenzenesulfonamide to form 1-[(4-chlorophenyl)phenylmethyl]-4-[(4-methylphenyl)sulfonyl]-piperazine, and removing the 4-methylbenzenesulfonyl group from the 1-[(4-chlorophenyl)phenylmethyl]-4-[(4-methylphenyl)sulfonyl]-piperazine to produce 1-[(4-chlorophenyl)phenylmethyl]piperazine.
The former method has a problem in that the optical resolution yield is as low as 13%. The latter method has a problem in that the method needs a plurality of expensive reagents and is tedious.
SUMMARY OF THE INVENTION
According to the present invention, optically active 1-[(4-chlorophenyl)phenylmethyl]piperazine can be efficiently produced in a good yield, by using industrially readily available compounds.
The present invention provides:
1. a composition comprising
an optical isomer of formula (1″):
wherein X denotes a chlorine atom, a C1-C3 alkyl group or a C1-C3 alkoxy group and * designate an asymmetric carbon atom, and
an enantiomer thereof, in an optional ratio;
2. a process for producing a racemic 4-(tert-butoxycarbonyl)piperazine compound of formula (1):
wherein X denotes a chlorine atom, a C1-C3 alkyl group or a C1-C3 alkoxy group, which comprises reacting 1-[(substituted phenyl) phenylmethyl]piperazin of formula (4):
wherein X has the same meaning as defined above, with di-tert-butyl dicarbonate of formula (5):
[(CH
3
)
3
COCO]
2
O (5);
3. an adduct salt of formula (3):
wherein X denotes a chlorine atom, a C1-C3 alkyl group or a C1-C3 alkoxy group and * designate an asymmetric carbon atom, n represents an integer of 1 or 2, and Z represents
an optically active acid of formula (2):
wherein L represents —COOH or —SO
3
H,
R
2
represents a hydrogen atom or a hydroxyl group,
R
1
and R
3
are the same or different and each independently represent
a hydrogen atom, a halogen atom, an arylcarbonyloxy group,
a liner or branched alkyl group which may be substituted with at least one group selected from a hydroxyl group, a halogen atom, arylcarbonyloxy, carboxy and arylaminocarbonyl;
an aryl group which may be substituted with at least one group selected from a halogen atom, alkyl and alkoxy;
an aralkyl group which may be substituted with at least one group selected from a halogen atom, alkyl, alkoxy and a hydroxyl group;
an aryloxy group which may be substituted with at least one group selected from a halogen atom, alkyl, alkoxy and a hydroxyl group;
a cyclic alkyloxy group which may be substituted with at least one group selected from a halogen atom, alkyl, alkoxy or a hydroxyl group; or
a cyclic alkyl group which may be substituted with at least one group selected from a halogen atom, alkyl, alkoxy, a hydroxyl group and a phenylcarbonylamino group; or
R
1
and R
3
may be bonded together to form
an alkylene group which may be substituted with at least one group selected from a halogen atom, an alkyl alkoxy, carboxyl, oxo, hydroxyl, and a phenylcarbonylamino group; or
a heterocycle which may be substituted with at least one group
selected rom an alkyl group, alkoxy or a halogen atom;
4. a process for producing the adduct salt of formula (3) as defined above, which comprises reacting a composition comprising an optical isomer of 4-(tert-butoxycarbonyl)piperazine compound of formula (1″) as defined above and an enantiomer thereof, with an optically active acid of formula (2) as defined above;
5. a process for producing an adduct salt of formula (6):
wherein X denotes a chlorine atom, a C1-C3 alkyl group or a C1-C3 alkoxy group, * represents an asymmetric carbon atom, and n represents an integer of 1 or 2,
Y represents a halogen atom, —OSO
3
H, —OSO
2
CH
3
, —OCOCF
3
, —OCOCH
3
and —OCOH, which comprises reacting an optically active 4-(tert-butoxycarbonyl)piperazine of formula (1′) as defined above with an acid of formula: HY, wherein Y represents the same as defined above; and
6. a process for producing an optically active 1-[(substituted phenyl)phenylmethyl]piperazine of formula (7):
wherein X and * each have the same meaning as defined above, which process comprises reacting an optically active 4-(tert-butoxycarbonyl)piperazine compound of formula (1′) as defined above, with an acid, and optionally subsequently with a base.
REFERENCES:
patent: 2819269 (1958-01-01), Weston et al.
patent: 5478941 (1995-12-01), Cossement et al.
patent: 5703082 (1997-12-01), Cossement et al.
patent: 5792770 (1998-08-01), Cossement et al.
patent: 2 225 321 (1990-05-01), None
patent: 7-2816 (1995-01-01), None
Plobeck et al., J.Med.Chem. vol. 43,p. 3878-3894 (2000).*
C.J. Opalka et al., “A Novel Synthesis of the Enantiomers of an Antihistamine Drug by Piperazine Formation from a Primary Amine”, Synthesis, (1995), pp. 766-768.
G.R. Clemo et al., “The Optical Rotatory Powers of Some 4-Substituted Benzhydrylamines”, J. Chem. Soc., (1939), pp. 1958-1960.
Hirata Norihiko
Kudo Junko
Yoshida Tomoyasu
Bernhardt Emily
Sumitomo Chemical Company Limited
LandOfFree
Optically active 4-(tert-butoxycarbonyl)piperazine compound,... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Optically active 4-(tert-butoxycarbonyl)piperazine compound,..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Optically active 4-(tert-butoxycarbonyl)piperazine compound,... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3329700