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Synthesis method of 8-hydroxyl ethyl caprylate

A technology of ethyl hydroxyoctanoate and a synthetic method, which is applied in the field of synthesis of pharmaceutical intermediates, can solve problems such as high raw material prices, complex processes, and long reaction routes, and achieve the advantages of industrial production, simplified process steps, and convenient source of raw materials Effect

Active Publication Date: 2013-08-07
JIANGSU BOTAI PHARMA COMPANY
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0008] The reaction yield of the first method is low; 5-hexen-1-alcohol and ethyl 2-methylthioacetate raw material prices are high in the second method; 6-bromohexanol is first used dihydropyran in the third method Protection, followed by condensation, decarboxylation and esterification reactions, the reaction route is long and the process is complicated
[0009] Therefore, the preparation process of ethyl 8-hydroxyoctanoate is more complicated in the prior art, and raw material cost is high

Method used

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  • Synthesis method of 8-hydroxyl ethyl caprylate
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  • Synthesis method of 8-hydroxyl ethyl caprylate

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[0031] The synthetic method of 8-hydroxy octanoic acid ethyl ester of the present invention, as Figure 4 as shown, Figure 4 It is a schematic flow sheet of the synthetic method of 8-hydroxyoctanoic acid ethyl ester of the present invention, comprising:

[0032] Step 101, dissolving 6-bromohexanol and diethyl malonate in an azeotropic organic solvent and performing a heating reaction under alkali catalysis to generate an intermediate, which is 2-(6-hydroxyhexyl) Diethyl malonate, wherein the molar ratio of 6-bromohexanol, diethyl malonate and base is 1:0.95~1.05:1.37~2.73;

[0033] Step 102, dissolving the intermediate in a polar aprotic solvent and water under the catalysis of sodium halide for heating reaction to generate ethyl 8-hydroxyoctanoate, wherein the molar ratio of the intermediate to sodium halide is 1 : 1~3.

[0034] In the embodiment of the present invention, first, 6-bromohexanol and diethyl malonate are reacted under alkali catalysis, and hydrogen bromide i...

Embodiment 1

[0047] Step 1, add 6-bromohexanol 132.5g, diethyl malonate 119g in the four-necked flask of 1000ml, alkali selects potassium carbonate 195g, wherein, 6-bromohexanol, diethyl malonate and potassium carbonate The molar ratio is 1:1.016:1.93. The azeotropic organic solvent is 120ml of N,N-dimethylformamide (DMF) and 250ml of cyclohexane, and the temperature is raised to 80°C for reflux reaction, and the reaction is determined by gas chromatography. After completion, it was lowered to room temperature, and the filter cake and filtrate were obtained by suction filtration. The filtrate was concentrated to dryness, diluted with 200ml ethyl acetate, washed with water, and concentrated to obtain 175g of yellow oily liquid, i.e. intermediate 2-(6-hydroxyhexyl) Diethyl malonate, the molar yield is 90%;

[0048] Step 2. Dissolve the product obtained in the previous step in 300ml of dimethyl sulfoxide, add 46g of sodium chloride and 23g of water, raise the temperature to 145°C, keep the te...

Embodiment 2

[0051] Step 1. Add 132.5 g of 6-bromohexanol, 119 g of diethyl malonate, and 212 g of sodium carbonate in a 1000 ml four-necked flask, wherein 6-bromohexanol, diethyl malonate and sodium carbonate The molar ratio is 1:1.016:2.73, 150ml of N,N-diethylformamide and 250ml of n-hexane are selected as the azeotropic organic solvent, and the temperature is raised to 150°C for reflux. After the reaction is judged by gas chromatography, it is cooled to room temperature. Suction filtration obtains filter cake and filtrate, and filtrate is concentrated dry, is diluted with 200ml ethyl acetate, then washes with water, concentrates, obtains 167g yellow oily liquid, i.e. intermediate 2-(6-hydroxyhexyl) diethyl malonate, Molar yield is 86%;

[0052] Step 2. Dissolve the product obtained in the previous step in 250ml of dimethyl sulfoxide, add 78g of sodium bromide and 30g of water, raise the temperature to 100°C, keep the temperature for 8 hours, then cool down to 20°C, and use 200ml of ace...

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Abstract

The invention relates to the synthesis technical field of medical intermediates and discloses a synthesis method of 8-hydroxyl ethyl caprylate. The synthesis method comprises the following steps of: dissolving 6-bromohexanol and diethyl malonate in an azeotropic organic solvent, heating to have reaction under alkaline catalysis to generate an intermediate which is 2-(6-hydroxyl hexyl) diethyl malonate, wherein the molar ratio of 6-bromohexanol to diethyl malonate to alkali is 1:0.95-1.05:1.37-2.73; and dissolving the intermediate in a polar aprotic solvent and water, heating to having reaction under catalytic effect of sodium halide to generate 8-hydroxyl ethyl caprylate, wherein the molar ratio of the intermediate to sodium halide is 1:1-3. According to the technical scheme provided by the invention, the process line is simple and the cost of raw materials is low; therefore and the method is favorable to industrial production.

Description

technical field [0001] The invention relates to the technical field of synthesis of pharmaceutical intermediates, in particular to a synthesis method of ethyl 8-hydroxyoctanoate. Background technique [0002] Ethyl 8-hydroxyoctanoate is a compound commonly used in pharmaceutical production. [0003] The synthetic method of the 8-hydroxy octanoic acid ethyl ester disclosed in the prior art has following several kinds at present: [0004] The first one, researchers such as Kudo, reported in the "Synlett" journal (Synlett, 23(12), 1843-1846; 2012) that caprylic lactone and ethanol were reacted under the catalysis of sulfuric acid to obtain ethyl 8-hydroxyoctanoate, which Synthetic route such as figure 1 Shown, its yield is 44%. [0005] The second, Deng and other researchers reported on the "Tetrahedron Letters" journal (Tetrahedron Letters, 38 (45), 7829-7832; 1997) with 5-hexen-1-alcohol and 2-methylthioethyl acetate to Acetonitrile is used as a solvent to obtain ethyl 8-...

Claims

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Application Information

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IPC IPC(8): C07C69/675C07C67/32
Inventor 童华光
Owner JIANGSU BOTAI PHARMA COMPANY
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