Process for the preparation of tetronic acid

Abstract

Tetronic acid of following Formula (2): is industrially efficiently prepared through a reaction of 4-hydroxy- or 4-alkoxy-acetoacetic acid or an ester thereof of following Formula (1): wherein R<1> and R<2> each independently represent a hydrogen atom or an alkyl group, by carrying out the reaction in the presence of an organic solvent and an acid but substantially in the absence of water. Producttetronic acid is useful as an intermediate for fine chemicals such as pharmaceuticals, agricultural chemicals, and semiconductor resist polymers.

Description

technical field

[0001] The present invention relates to a method for preparing tetronic acid, which is useful as a fine chemical intermediate for medicines, agricultural chemicals, etc., and as an intermediate for semiconductor resist polymers. Background technique

[0002] Traditionally, as the preparation method of tetronic acid, following method is known: make 4-tert-butoxyacetoacetate ethyl ester and hydrochloric acid aqueous solution react, then prepare tetronic acid by evaporating to dryness to hydrochloric acid aqueous solution (patent Literature 1, 2). However, tetronic acid is a water-soluble compound, so if water is used in the reaction, it must be concentrated and dried to obtain tetronic acid in the form of crystals. In this method, a very large amount of energy is required for concentrating a large amount of water, so it is difficult to say that it is a beneficial method on an industrial scale.

[0003] In addition, Patent Document 3 describes a method of deri...

Examples

Embodiment 1

[0073] Sodium tert-butoxide (53.7 g, 0.559 mol) was suspended in tetrahydrofuran (429 g), and a mixed solution of ethyl 4-chloroacetoacetate (40.0 g, 0.243 mol) and tetrahydrofuran (71.0 g) was added dropwise thereto and The temperature was made to be in the range of 20 to 30°C, and after completion of the dropwise addition, it was stirred at room temperature (25°C) for 20 hours. After concentrating tetrahydrofuran, an aqueous hydrochloric acid solution (a mixture of 34.4 g of 35% hydrochloric acid and 200 g of water) was added dropwise under ice cooling, followed by extraction with ethyl acetate and liquid separation. The organic layer was washed with water and then concentrated to obtain ethyl 4-tert-butoxyacetoacetate (yield 43.1 g, weight yield 87.7%, purity 76.6%).

[0074] Ethyl 4-tert-butoxyacetoacetate 1 H-NMR spectrum (CDCl 3 ): δ1.21(s, 9H), 1.27(t, 3H), 3.55(s, 2H), 4.01(s, 2H), 4.19(q, 2H)

[0075] The obtained ethyl 4-tert-butoxyacetoacetate (40 g, 0.152 mol (i...

Embodiment 2

[0077] The same method as in Example 1 was used to obtain ethyl 4-tert-butoxyacetoacetate.

[0078] The obtained ethyl 4-tert-butoxyacetoacetate (10 g, 0.0399 mol (in terms of purity)) was dissolved in acetic acid (21.1 g), and hydrogen chloride gas (0.0867 mol) was blown in at a temperature of 20 to 30°C. After blowing in, it stirred at room temperature (25 degreeC) for 1 hour. The reaction liquid was decompressed with a rotary evaporator, the residual hydrogen chloride gas was degassed, and the low boiling point substances and acetic acid were distilled off, and concentrated until the residual acetic acid amount was 1 / 2 (10.55 g) of the added amount. The residue was stirred to precipitate crystals, ethyl acetate (9 g) was added dropwise thereto, and the mixture was stirred at room temperature (25° C.) for 2 hours. Then, the crystal was taken out by filtration to obtain tetronic acid (yield 1.92g, yield 47.5%, purity 99.2%)

technical field

[0001] The present invention relates to a method for preparing tetronic acid, which is useful as a fine chemical intermediate for medicines, agricultural chemicals, etc., and as an intermediate for semiconductor resist polymers. Background technique

[0002] Traditionally, as the preparation method of tetronic acid, following method is known: make 4-tert-butoxyacetoacetate ethyl ester and hydrochloric acid aqueous solution react, then prepare tetronic acid by evaporating to dryness to hydrochloric acid aqueous solution (patent Literature 1, 2). However, tetronic acid is a water-soluble compound, so if water is used in the reaction, it must be concentrated and dried to obtain tetronic acid in the form of crystals. In this method, a very large amount of energy is required for concentrating a large amount of water, so it is difficult to say that it is a beneficial method on an industrial scale.

[0003] In addition, Patent Document 3 describes a method of deri...

Examples

Embodiment 1

[0073] Sodium tert-butoxide (53.7 g, 0.559 mol) was suspended in tetrahydrofuran (429 g), and a mixed solution of ethyl 4-chloroacetoacetate (40.0 g, 0.243 mol) and tetrahydrofuran (71.0 g) was added dropwise thereto and The temperature was made to be in the range of 20 to 30°C, and after completion of the dropwise addition, it was stirred at room temperature (25°C) for 20 hours. After concentrating tetrahydrofuran, an aqueous hydrochloric acid solution (a mixture of 34.4 g of 35% hydrochloric acid and 200 g of water) was added dropwise under ice cooling, followed by extraction with ethyl acetate and liquid separation. The organic layer was washed with water and then concentrated to obtain ethyl 4-tert-butoxyacetoacetate (yield 43.1 g, weight yield 87.7%, purity 76.6%).

[0074] Ethyl 4-tert-butoxyacetoacetate 1 H-NMR spectrum (CDCl 3 ): δ1.21(s, 9H), 1.27(t, 3H), 3.55(s, 2H), 4.01(s, 2H), 4.19(q, 2H)

[0075] The obtained ethyl 4-tert-butoxyacetoacetate (40 g, 0.152 mol (i...

Embodiment 2

[0077] The same method as in Example 1 was used to obtain ethyl 4-tert-butoxyacetoacetate.

[0078] The obtained ethyl 4-tert-butoxyacetoacetate (10 g, 0.0399 mol (in terms of purity)) was dissolved in acetic acid (21.1 g), and hydrogen chloride gas (0.0867 mol) was blown in at a temperature of 20 to 30°C. After blowing in, it stirred at room temperature (25 degreeC) for 1 hour. The reaction liquid was decompressed with a rotary evaporator, the residual hydrogen chloride gas was degassed, and the low boiling point substances and acetic acid were distilled off, and concentrated until the residual acetic acid amount was 1 / 2 (10.55 g) of the added amount. The residue was stirred to precipitate crystals, ethyl acetate (9 g) was added dropwise thereto, and the mixture was stirred at room temperature (25° C.) for 2 hours. Then, the crystal was taken out by filtration to obtain tetronic acid (yield 1.92g, yield 47.5%, purity 99.2%)

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