GB2038824A - Preparation of 3-methyl-2- (carboxy-???-hydroxyethylamido)- quinoxaline-1,4-dioxides - Google Patents

Abstract

A process for preparing 3- methyl-2-(carboxy-???- hydroxyethylamido)-quinoxaline-1,4- dioxide by reacting benzofuroxane with the in situ prepared product of the reaction of an alkyl acetoacetic ester with monoethanolamine.

Description

SPECIFICATION Preparation of 3-Methyl-2-(carboxy-ss- Hydroxyethylamido)-Quinoxaline-1 ,4Dioxides The invention relates to a process for preparing a 3-methyl-2-(carboxy-13-hydroxyethylamido)- quinoxaline-1 ,4-dioxide e.g. of the structural formula:

from a benzofuroxane.

French Patent specification No. 1,594,628 discloses methods for preparing the compound (1) and other similar products from benzofuroxane and acetoa ncccetic acid amides, said amides being prepared from amines and diketene. The latter chemical is highly toxiic aaand its use entails explosion risk.

According to the invention the benzofuroxane is reacted in situ with the product prepared by reaction of alkyl acetoacetic ester with monoethanolamine, an excess of the latter conveniently being provided to constitute a reaction medium.

This process has the advantages of preparation of the product in a single stage, starting from easily obtainable materials which are nonexplosive, have a low level of toxicity and hazard, and are easy to handle on an industrial scale. The yield can be 53% of good quality product.

The product yield is not specified in the above mentioned French patent specification No.

1,594,628, but tests performed in the laboratory following the conditions disclosed in its example gave yields of 42% raw product and 3035% of crystallised product.

The reaction scheme of a process according to the invention is as follows:

where R is an alkyl group, preferably a methyl or ethyl group.

The reaction of an alkyl acetoacetic ester with monoethanolamine provides an alkyl 3-(,- hydroxyethylamino)-crotoneate which is reacted in situ with the benzofuroxane to provide 3 methyl-2-(ca rboxy-l3-hydroxyethyla m ido)- quinoxaline-1 ,4-dioxide.

Example 1 20 parts by weight of methyl acetoacetate were added over a period of one to two hours, with stirring, to 200 parts by weight of monoethanolamine, so that the temperature did not exceed 60"C. The mixture was gradually cooled over a period of one hour down to 300C and 140 parts by weight of benzofuroxane were added. The mixture was stirred for 24 hours with the temperature being held to between 30"C and 350C. At the end of the reaction, the mixture was cooled to 200C and the product was removed by filtration. It was washed with methanol and dried.

144 parts of 3-methyl-2-(carboxy-l3- hydroxyethylamido)-quinoxaline- 1 4-dioxide were obtained, which product may be purified by recrystallisation in ethanol/water (50%) to a constant melting point of 2090C.

Claims

1. A process for preparing a 3-methyl-2 (ca rboxy-p-hydroxyethyla m ido)-qu inoxaline- 1,4- dioxide in which the product obtained by reaction of alkyl acetoacetic ester with monoethanolamine is reacted in situ with a benzofuroxane.

2. A process according to claim 1 wherein the reaction product of alkyl acetoacetate with excess monoethanolamine is reacted in situ with the benzofuroxane.

3. A process according to claim 1 or 2 wherein the alkyl acetoacetate comprises methyl or ethyl acetoacetate.

4. A process for preparing a 3-methyl-2 (carboxy--hyd roxyethylam ido)-quinoxaIine- 1 ,4- dioxide, the process being substantially as hereinbefore described in the Example.

5. A 3-methyl-2-(carboxy-ss- hydroxyethylamido)-quinoxaline-l ,4-dioxide obtained by a process according to any of claims 1 to 4.

**WARNING** end of DESC field may overlap start of CLMS **.

Claims (5)

**WARNING** start of CLMS field may overlap end of DESC **. SPECIFICATION Preparation of 3-Methyl-2-(carboxy-ss- Hydroxyethylamido)-Quinoxaline-1 ,4Dioxides The invention relates to a process for preparing a 3-methyl-2-(carboxy-13-hydroxyethylamido)- quinoxaline-1 ,4-dioxide e.g. of the structural formula: from a benzofuroxane. French Patent specification No. 1,594,628 discloses methods for preparing the compound (1) and other similar products from benzofuroxane and acetoa ncccetic acid amides, said amides being prepared from amines and diketene. The latter chemical is highly toxiic aaand its use entails explosion risk. According to the invention the benzofuroxane is reacted in situ with the product prepared by reaction of alkyl acetoacetic ester with monoethanolamine, an excess of the latter conveniently being provided to constitute a reaction medium. This process has the advantages of preparation of the product in a single stage, starting from easily obtainable materials which are nonexplosive, have a low level of toxicity and hazard, and are easy to handle on an industrial scale. The yield can be 53% of good quality product. The product yield is not specified in the above mentioned French patent specification No. 1,594,628, but tests performed in the laboratory following the conditions disclosed in its example gave yields of 42% raw product and 3035% of crystallised product. The reaction scheme of a process according to the invention is as follows: where R is an alkyl group, preferably a methyl or ethyl group. The reaction of an alkyl acetoacetic ester with monoethanolamine provides an alkyl 3-(,- hydroxyethylamino)-crotoneate which is reacted in situ with the benzofuroxane to provide 3 methyl-2-(ca rboxy-l3-hydroxyethyla m ido)- quinoxaline-1 ,4-dioxide. Example 1 20 parts by weight of methyl acetoacetate were added over a period of one to two hours, with stirring, to 200 parts by weight of monoethanolamine, so that the temperature did not exceed 60"C. The mixture was gradually cooled over a period of one hour down to 300C and 140 parts by weight of benzofuroxane were added. The mixture was stirred for 24 hours with the temperature being held to between 30"C and 350C. At the end of the reaction, the mixture was cooled to 200C and the product was removed by filtration. It was washed with methanol and dried. 144 parts of 3-methyl-2-(carboxy-l3- hydroxyethylamido)-quinoxaline- 1 4-dioxide were obtained, which product may be purified by recrystallisation in ethanol/water (50%) to a constant melting point of 2090C. Claims

1. A process for preparing a 3-methyl-2 (ca rboxy-p-hydroxyethyla m ido)-qu inoxaline- 1,4- dioxide in which the product obtained by reaction of alkyl acetoacetic ester with monoethanolamine is reacted in situ with a benzofuroxane.

2. A process according to claim 1 wherein the reaction product of alkyl acetoacetate with excess monoethanolamine is reacted in situ with the benzofuroxane.

3. A process according to claim 1 or 2 wherein the alkyl acetoacetate comprises methyl or ethyl acetoacetate.

4. A process for preparing a 3-methyl-2 (carboxy--hyd roxyethylam ido)-quinoxaIine- 1 ,4- dioxide, the process being substantially as hereinbefore described in the Example.

5. A 3-methyl-2-(carboxy-ss- hydroxyethylamido)-quinoxaline-l ,4-dioxide obtained by a process according to any of claims 1 to 4.