Process of production of 4-substituted-3-halogeno-1,4-benzoxazep

Details Process of production of 4-substituted-3-halogeno-1,4-benzoxazep Process of production of 4-substituted-3-halogeno-1,4-benzoxazep

1999-11-24

2000-09-05

Powers, Fiona T.

Organic compounds -- part of the class 532-570 series

Organic compounds

Unsubstituted hydrocarbyl chain between the ring and the -c-...

540487, C07D26714, C07D41312, C07D41314

Patent

active

06114522&

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to process for the production of a 4-substituted-3-halogeno-1,4-benzoxazepine derivative and the salts thereof, which are useful as a pharmaceutical or as a starting material or intermediate for the synthesis thereof.


BACKGROUND ART

A 4-substituted-3-halogeno-1,4-benzoxazepine derivative is an important compound usable as a pharmaceutical for psychoneurotic disorders such as anxiety neurosis, phobias, obsessive-compulsive disorders, schizophrenia, post-cardiac trauma stress disorders, depression disorders, and psychosomatic disorders, disorders such as eating disorders, menopausal disorders, infantile autism and also emesis or disorders involving the cerebral circulatory system accompanying cerebral infarction and cerebral hemorrhaging or as a synthetic starting material or an intermediate of pharmaceuticals etc. However, industrial processes for production thereof which have been fully satisfactory in terms of the operability and yield, are not known in the art.
A process for synthesis of a 4-substituted-3-halogeno-1,4-benzoxazepine derivative is disclosed in, for example, International Publication WO96-24594. That is, this process comprises reacting a benzoxazepine derivative with an acid chloride such as phosphorus oxychloride (POCl.sub.3), thionyl chloride (SOCl.sub.2), while adding acid such as hydrochloric acid or a base such as N,N-diethylaniline, if necessary. However, in this process, since a large amount of acid chloride is used, there is the accompanying risk of the generation of hydrochloric acid gas and a sudden rise in temperature and the generation of bumping, etc. in the neutralization reaction for treatment and decomposition of the excessive acid chloride and, therefore, there was the industrial difficulty. Further, in terms of the yield as well, the yield was 30 to 60%--which cannot be necessarily said to be good. Further, there was the problem that the benzoxazepine derivative starting material would remain in the reaction solution in considerable amounts and it was difficult to separate the starting material compound and the target compound.
In this way, no process has been known which has been fully satisfactory for the industrial production of a 4-substituted-3-halogeno-1,4-benzoxazepine derivative. Therefore, a new process for production of a 4-substituted-3-halogeno-1,4-benzoxazepine derivative is necessary to be developed.


SUMMARY OF THE INVENTION

Accordingly, an object of the present invention is to provide a new process for production of a 4-substituted-3-halogeno-1,4-benzoxazepine derivative and the salts thereof which are easy to operate and which are industrially satisfactory and which are good yield.
Another object of the present invention is to provide an industrially satisfactory process for production of a benzoxazepine derivative and the salts thereof using the above process.
In accordance with the present invention, there is provided a 4-substituted-3-halogeno-1,4-benzoxazepine derivative having the formula (I): ##STR4##
wherein, R indicates a hydrogen atom, halogen atom, C.sub.1 to C.sub.4 lower alkyl group, C.sub.1 to C.sub.4 lower alkoxy group, or hydroxy group, preferably a hydrogen atom or halogen atom, and A indicates a C.sub.2 to C.sub.5 halogenoalkyl group or a group having the formula (III): ##STR5##
wherein, n is an integer of 2 to 5, the dotted line indicates the presence or absence of a bond, W indicates a carbon atom, methine, methylene, or nitrogen atom, where when W is a nitrogen atom, Z bonds with W and the dotted line indicates the absence of a bond, and Z indicates an aromatic hydrocarbon group which may be substituted, or a heterocyclic group which may be substituted, preferably a C.sub.2 -C.sub.5 halogenoalkyl group or a group having the formula (XXVI) or (XXVII): ##STR6## wherein n is an integer of 2 to 5, Ar is a phenyl group, 2-pyridyl group or 2-pyrimidinyl group, X indicates a chlorine atom or bromine atom, preferably a chlorine atom, can be produced by deprotonizing, using a base, a benzoxazep

REFERENCES:
Lee et al, "The Reaction of Vinyl Phosphates and Iodotrimethylsilane: Synthesis of Vinyl Iodides from Ketones", Tetrahedron Letters, vol. 34, No. 15, pp. 2433-2436, Apr. 9, 1993.

Affiliated with

Also associated with

Rating

Process of production of 4-substituted-3-halogeno-1,4-benzoxazep 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 of production of 4-substituted-3-halogeno-1,4-benzoxazep, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process of production of 4-substituted-3-halogeno-1,4-benzoxazep will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2213480