(R)-3-Piperidinamine dihydrochloride, as first-hand compound, is an important synthetic intermediate of chemical and pharmaceutical drugs. It has an important application in the chemical and pharmaceutical community. Important intermediates in the value of medicine and chemical auxiliary, the pharmaceutical industry is mainly used to synthesize di-peptidase IV (DPP-IV) inhibitors, such as Togrein, Agline and other diabetic drugs. The market demand is large. It has certain research significance.
CAS 334618-23-4 mainly has the following synthetic methods: 1. The starting raw material with 3-amino pyridine as the starting raw material, which is catalyzed by catalytic hydride to obtain 3-amino pyrine, and then use it. The handicapped reagent is split and obtained (R) -3-amino pyrine. This method is low in accordance with the catalytic reduction of 3-amino pyridine and expensive catalysts. The starting raw material is based on D-oline hydrochloride, reacts with dichlinels between -78-45 ° C, and then exchange resin through a strong alkaline anion to obtain (R) -3-Amino-2- Rough ketone, after purification, is restored to (R) -3-aminoprimidine through lialh4, and finally forming salt hydrochloride. The price of birdine is expensive, and the response is performed under the condition of deep low temperature (-78 ° C). It is poorly operable. At the same time, the tetrahydrine and aluminum lithium that is easily exploded is used to increase the operating cost. Hydrogenation restore, BOC protection, HOFman degradation, hand -splitting, and removing protection into hydrochloride. This step is more milder than the previous routes. Although the conditions are harsh in catalytic hydrogenation of nicotinamide, it is very large. Improvement space; 4. 3-pyrine metamamide that is removed outside the outside is the raw material. The bacteria (cupriavidussp. KNK-J915) decompose (s) -3-pyrimamide to get (R) -3-Piopidine armor Amide, then the BOC protection of amino groups, HOFMAN degradation, and removing protection into hydrochloride. This method is relatively novel. The R -shaped heterogeneous body, but the separation process of bacterial decomposition is very high, and the operating cost is large. At present, it is difficult to achieve large -scale industrial production.
The reagent is used as a heterocyclic dilate N-gifumin reaction; the synthesis replace the reactor that replaces olone, which can reduce the risk of optical toxicity.
