Process for the preparation of thiazole intermediate

Details Process for the preparation of thiazole intermediate Process for the preparation of thiazole intermediate

2002-12-05

2004-12-21

Desai, Rita (Department: 1626)

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

active

06833459

ABSTRACT:

FIELD OF THE INVENTION
The present invention provides a process for the preparation of thiazole derivative. More particularly, the present invention relates to a process for the preparation of 4-methyl-5-formyl-thiazole of the formula (I).
4-Methyl-5-formyl-thiazole of the formula (I) is a useful key intermediate in the preparation of Cefditoren pivoxil of the formula (II), which is a well known antibiotic.
BACKGROUND OF THE INVENTION
Harrington et al (J. Chem. Soc., (1939) 443-446) described a process for the preparation of 4-methyl-5-formyl-thiazole of the formula (I), starting from ethyl 4-methylthiazole-5-carboxylate which was converted through the amide to the nitrile, which in turn was converted to the aldehyde. The process involves the preparation of the nitrile compound by using POCl
3
, which is highly corrosive, hazardous and difficult to handle in large scales.
Yokoyama et al (Stud. Surf. Sci. Catal., (1994), 90, 47-58) reports a process for the direct hydrogenation of aromatic carboxylic acid to the corresponding aldehydes. The catalyst used is modified zirconia.
EP patent number 0 343 640 claims a process for the preparation of heterocyclic aldehyde from the corresponding carboxylic acid and its derivatives using a catalyst consisting of an oxide of Zinc, Yitrium, lanthanides or Group 4A elements. The oxides of these metals are prepared at very high temperature such as 200 to 900° C. Methyl 4-methylthiazole-5-carboxylate was hydrogenated using an oxide catalyst composed of chromium, zirconium to produce 4-methylthiazole-5-carboxaldehyde also at very high temperature ranging from 200 to 700° C., which makes the process industrially non-workable.
JP 45036908 discloses a process for the preparation of 4-methyl-5-hydroxymethyl thiazoles from 4-methyl-5-(ethoxycarbonyl) thiazoles using LiAlH
4
and diethylether. The process suffers the following disadvantages: The reducing agent, LiAlH
4
cannot be handled in the large operations as it is an hazardous reagent. This problem has been overcome by the use of sodium borohydride, in the presence of AlCl
3
in the present invention as the rate of evolution of hydrogen in the process is controllable and hence, the reaction as a whole is easy to handle.
To overcome the problems associated in the preparation of 4-methyl-5-formyl-thiazole of the formula (I), we focussed our research to develop a process, which uses non-hazardous materials, industrially workable at ambient temperature and safe to use.
OBJECTIVE OF THE INVENTION
The main objective of the present invention is to provide a process for the preparation of 4-methyl-5-formyl-thiazole of the formula (I), which is useful as an intermediate in the preparation of Cefditoren.
Another objective of the present invention is to provide a process for the preparation of 4-methyl-5-formyl-thiazole of the formula (I), which is commercially viable, high yielding, and with high purity of the product.
SUMMARY OF THE INVENTION
The present invention relates to a process for the preparation of 4-methyl-5-formyl-thiazole of the formula (I)
which comprises oxidising the 4-methyl-5-hydroxymethyl thiazole of the formula (IV) to 4-methyl-5-formyl-thiazole of the formula (I), using an oxidizing agent at a temperature in the range of −10° C. to 50° C., in the presence of a solvent.
In another embodiment of the present invention, there is a provided a process for the preparation of 4-methyl-5-hydroxymethyl thiazole of the formula (IV), which comprises reducing the thiazole ester of the formula (III), wherein R represents (C
1
-C
4
) alkyl group such as methyl, ethyl, n-propyl, iso-propyl, tert-butyl to 4-methyl-5-hydroxymethyl thiazole of the formula (IV), using sodium borohydride in the presence of AlCl
3
and a solvent, at a temperature in the range of −20° C. to 90° C.
The reaction scheme described above is as shown below.


REFERENCES:
patent: 0 343 640 (1994-10-01), None
patent: 45-36908 (1970-11-01), None
Sinha et al, 2002, CAS:137:234008.

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