Method for synthesizing (3R,5S)-6-chloro-3,5-dihydroxyhexanoate

Abstract

The invention discloses a method for synthesizing (3R,5S)-6-chloro-3,5-dihydroxyhexanoate, wherein the method comprises the following steps: preparing 4-chloro-3-hydroxybutyrate; preparing tert-butyl (S)-6-chloro-5-hydroxy-3-oxo-hexanoate from the 4-chloro-3-hydroxybutyrate; adding proper amount of pure water to a reaction kettle as a solvent and adding hydrophosphate to prepare a pH buffer solution which is 0.05mol / L-0.15mol / L in molar concentration, so as to generate a (3R,5S)-6-chloro-3,5-dihydroxyhexanoate solution with the presence of a biological catalyst and a hydrogen donor, and reacting at 45-55 DEG C for 10-15h; and after reaction, sequentially filtering, extracting, decompressing and concentrating, and rectifying so as to obtain a finished (3R,5S)-6-chloro-3,5-dihydroxyhexanoate product; the mass-volume concentration of the (3R,5S)-6-chloro-3,5-dihydroxyhexanoate is 8g / mL-17g / mL, and the dosage of carboxyl reductase is 4-6% of the (3R,5S)-6-chloro-3,5-dihydroxyhexanoate. The method disclosed by the invention not only is capable of reducing production cost and is conducive to energy conservation and emission reduction, but also is higher in molar yield from a production reaction process.

Description

technical field [0001] The invention relates to a compound preparation method, in particular to a preparation method of (3R,5S)-6-chloro-3,5-dihydroxyhexanoic acid tert-butyl ester. Background technique [0002] Currently, tert-butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate is produced by chemical synthesis as follows: Catalytic reduction of (S)-6-chloro-5-hydroxy-3 -(3R,5S)-6-chloro-3,5-dihydroxyhexanoic acid tert-butyl ester obtained from tert-butyl carbonylhexanoate, the (3R,5S)-6-chloro- 3,5-dihydroxyhexanoic acid tert-butyl ester is racemized, it needs to be subjected to chiral resolution, the molar yield is much lower than 50%, and expensive reagents need to be used; ,5S)-tert-butyl 6-chloro-3,5-dihydroxyhexanoate (chiral reduction), it needs to be at -80~-100°C to have better optical selectivity, otherwise the isomer impurities will be It will be as high as more than 15%. Such a low temperature can only be realized by liquid nitrogen cooling. Therefore, the equipment...

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Problems solved by technology

[0002] Currently, tert-butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate is produced by chemical synthesis as follows: Catalytic reduction of (S)-6-chloro-5-hydroxy-3 -(3R,5S)-6-chloro-3,5-dihydroxyhexanoic acid tert-butyl ester obtained from tert-butyl carbonylhexanoate, the (3R,5S)-6-chloro- 3,5-dihydroxyhexanoic acid tert-butyl ester is racemized, it needs to be subjected to chiral resolution, the molar yield is much lower than 50%, and expensive reagents need to be used; ,5S)-tert-butyl 6-chloro-3,5-dihydroxyhexanoate (chiral reduction), it needs to be at -80~-100°C to have better optical selectivity, otherwise the isomer impurities will be It will be as high as more than 15%. Such a low temperature can only be realized by liquid nitrogen cooling. Therefore, the equipment requirements for industrialization will be very high, and the investment in these special equipment will be as high as more than 3 million yuan, the cost is very high, and in the preparation The liquid nitrogen process will consume a lot of electricity; in the actual production process, each ton of (3R,5S)-6-chloro-3,5-dihydroxyhexanoic acid tert-butyl needs to consume thousands of cubic meters of liquid nitrogen, This will consume a lot of power consumption, which is very unfavorable for energy saving and emission reduction