L-prolinol synthetic method

Abstract

The invention discloses an L-prolinol synthetic method. The method comprises the following steps that 1, ethyl alcohol is added in a reaction kettle, thionyl chloride is dropwise added at 10-15 DEG C, then, L-prolinol is added, the temperature is increased to 40 DEG C, a heat-preservation reaction is carried out for 10-12 h, the mixture is concentrated to be thick liquid after the reaction is finished, ethyl acetate is added for dissolution, the pH value is adjusted through triethylamine to be 7-8, and salt is filtered away to obtain L-proline ethyl ester; 2, the L-proline ethyl ester is in a methyl alcohol system, lithium chloride is added at 5-10 DEG C, the sodium borohydride is added many times, a heat-preservation reaction is carried out at 20-25 DEG C for 2-2.5 h, hydrochloric acid is added, heat-preservation hydrolysis is carried out for 2 h, methyl alcohol is recycled, the pH value is adjusted through 25% sodium hydroxide to be 12, a product is extracted through dichloromethane, anhydrous sodium sulfate drying is carried out, and filtering is carried out; 3, dichloromethane is recycled from mother liquid at 30-40 DEG C and normal pressure, oily matter is obtained, pressure reduction and distillation are carried out, and therefore the pure L-prolinol is obtained. According to the L-prolinol synthetic method, the reaction temperature is mild, the safety coefficient is low, no solid waste is produced, and environmental protection is achieved.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a synthesis method of L-prolinol. Background technique [0002] L-proline (referred to as proline) is one of the 18 kinds of amino acids that the human body synthesizes protein. It is also the main intermediate for the synthesis of first-line antihypertensive drugs such as captopril and enalapril. It has been widely used in food and pharmaceutical industries. It is colorless to white crystal or crystalline powder at normal temperature, slightly smelly, slightly sweet taste, easily soluble in water, insoluble in ethanol, insoluble in ether and n-butanol. The reduction product of L-proline, L-prolinol, is an important chiral chemical reagent, which is not only a raw material for the synthesis of excellent optical materials and chiral polymer materials, but also an important source of chirality for the synthesis of chiral drugs. With the rapid development of...

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Problems solved by technology

[0003] At present, there are two production methods of L-prolinol in the market: direct reduction method and indirect reduction method. The direct reduction method is to directly reduce L-proline with lithium tetrahydrogen. This route is not advisable in production. The current market The price of lithium aluminum tetrahydrogen is 1000-1200 / kg, while the price of L-prolinol is about 1200 / kg, the cost is too high to realize industrialization; in addition, there is also the use of metal pressurized catalytic reduction, but due to the metal The catalyst itself is relatively expensive and requires high pressure. Safety and environmental protection are very important issues. Due to cost and environmental protection considerations, it is even more difficult to achieve industrialized mass production.

The indirect reduction method uses L-proline as the raw material, and forms proline methyl ester through methyl esterification, but the yield is relatively low, and the post-treatment is troublesome, and the price of tetrahydrofuran is also relatively expensive, and it is difficult to control the cost

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