4-Chloro-4-methyl-5-methylene-1,3-dioxolane-2-one

Details 4-Chloro-4-methyl-5-methylene-1,3-dioxolane-2-one 4-Chloro-4-methyl-5-methylene-1,3-dioxolane-2-one

1984-11-16

1985-11-19

Milestone, Norma S.

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C07D31736

Patent

active

045543585

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

This invention relates to 4-chloro-4-methyl-5methylene-1,3-dioxolane-2-one which is a novel intermediate for the synthesis of 4-chloromethyl-5-methyl-1,3-dioxolene-2-one which, in turn, finds use as a modifying agent for making various prodrugs.


BACKGROUND ART

There are a number of drugs which, owing to chemical instability and poor bioavailability, find only limited uses as a medicament though they have potentially high pharmacological activities. One of means for improving these defects is to provide prodrugs by chemically modifying these drugs.
Japanese Patent Publication (Kokai) No. 57-26684 discloses a useful modifying agent for making such prodrugs consisting of a 1,3-dioxolene-2-one derivative of the formula: ##STR1## wherein R.sub.1 is a hydrogen atom, a lower alkyl or aryl, X is a halogen atom, and R.sub.2 is a hydrogen atom or a hydrocarbon chain forming a ring with R.sub.1. Specific compounds disclosed therein include 4-chloromethyl-5-methyl-1,3-dioxolene-2-one of the formula: ##STR2##


DISCLOSURE OF THE INVENTION

We have studied to provide a new method for preparing the above 4-chloromethyl-5-methyl-1,3-dioxolene-2-one (II). As a result, we have found that 4-chloro-4-methyl-5-methylene-1,3-dioxolane-2-one of the formula: ##STR3## surprisingly gives said objective compound (II) in a good yield by a rearrangement reaction which will be fully described hereinafter and accomplished the present invention.


PREFERRED EMBODIMENT OF THE INVENTION

4-Chloro-4-methyl-5-methylene-1,3-dioxolane-2-one (III) of the present invention is a novel compound. This compound may be easily prepared by reacting 4,5-dimethyl-1,3-dioxolene-2-one of the formula: ##STR4## with a chlorinating agent in an inert organic solvent normally under an ionic reaction condition.
The starting compound (IV) used herein is a known compound and may be synthesized by the method, for example, described in Tetrahedron Letters, 1701-1704 (1972).
Examples of inert organic solvents include chlorinated organic solvents such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like. Methylene chloride is most preferred.
Examples of chlorinating agents include sulfuryl chloride, chlorine gas and the like. Sulfuryl chloride is most preferred.
The molar ratio of chlorinating agent to the starting compound (IV) ranges preferably from about 0.9 to about 1.5, more preferably from about 1.0 to about 1.2. The use of chlorinating agent in amounts below said range or conversely in excess of said range results in a large amount of unreacted starting compound (IV) or a large amount of byproducts and thus is not preferable.
The reaction temperature ranges normally from 10.degree. C. to 80.degree. C., preferably from about 25.degree. C. to about 60.degree. C.
The reaction time may vary depending upon particular solvent and reaction temperature used and is generally from 30 minutes to 7 hours.
The compound (III) of this invention formed by the above-described reaction may be recovered and purified by a conventional method such as distillation in vacuo. Optionally, the reaction mixture containing the compound (III) may be used in the subsequent rearrangement reaction as such or after removing the solvent without isolating the compound (III).
Now the preparation of said 4-chloromethyl-5-methyl1,3-dioxolene-2-one (II) from the compound (III) of this invention will be described in detail.
The rearrangement of the compound (III) to the objective compound (II) may be carried out very easily by heating the compound (III) in the presence or absence of an inert organic solvent.
As examples of the above inert organic solvents, chlorinated organic solvents such as 1,2-dichloroethane, 1,1,2,2-tetrachloroethane and the like may be mentioned.
The heating temperature generally ranges from about 60.degree. C. to about 140.degree. C.
The reaction time may vary with particular temperature employed and is generally from about 1 hour to about 5 hours.
By effecting the rearrangement reaction under the above-described condition

REFERENCES:
patent: 4342693 (1982-08-01), Sakamoto et al.
Fischler et al, Tetrahedron Letters, No. 17 (1972) pp. 1701-1704.

Affiliated with

Also associated with

Rating

4-Chloro-4-methyl-5-methylene-1,3-dioxolane-2-one does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with 4-Chloro-4-methyl-5-methylene-1,3-dioxolane-2-one, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 4-Chloro-4-methyl-5-methylene-1,3-dioxolane-2-one will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-84612