807362-89-6Relevant academic research and scientific papers
CRYSTAL COMPRISING (2R)-2-PROPYLOCTANOIC ACID AND DIBENZYLAMINE
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Page/Page column 28, (2010/11/25)
According to the present invention, crystals comprising (2R)-2-propyloctanoic acid and an amine, which can be used as bulk drugs for safely orally administrable solid preparations with keeping the pharmacological effect, are provided. Among these crystals, the crystal with dibenzylamine per se is particularly useful as bulk drug for pharmaceuticals and can be used as an intermediate to produce (2R)-2-propyloctanoic acid having an optical purity of more than 99.5%e.e. which has not been obtained.
Process for producing (2r)-2-propyloctanoic acid and intermediate therefor
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Page/Page column 4-5, (2008/06/13)
The present invention relates to a process for producing (2R)-2-propyloctanoic acid, which comprises subjecting (2R)-2-hexyloxirane to a two-carbon adding reaction with ring-opening reaction, followed by a protecting reaction of a hydroxyl group to convert it to a compound represented by formula (I): (wherein X represents an optionally protected hydroxyl group) and then subjecting the compound to a one-carbon adding reaction to convert it to (2R)-2-propyloctanamide, followed by recrystallization and hydrolysis. According to the process of the present invention, (2R)-2-propyloctanoic acid can be produced by less steps as compared with the conventional method without a dangerous reaction.
A new process for synthesis of the astrocyte activation suppressor, ONO-2506
Hasegawa, Tomoyuki,Kawanaka, Yasufumi,Kasamatsu, Eichi,Ohta, Chisa,Nakabayashi, Kazuhiro,Okamoto, Masaki,Hamano, Masaya,Takahashi, Keiji,Ohuchida, Shuichi,Hamada, Yasumasa
, p. 774 - 781 (2012/12/26)
Development of a new process for the synthesis of ONO-2506, an agent that suppresses astrocyte activation, is described. Previous processes that involved asymmetric synthesis with a chiral auxiliary were unsatisfactory from a cost perspective because the relatively expensive chiral auxiliaries were not recyclable. To develop a more cost-effective process, we designed a new process starting from chiral 1,2-epoxyoctane, which was readily prepared catalytically by Prof. Jacobsen's method. The new five-step process was developed with the establishment of a modified cyanation condition, in which lithium cyanide was prepared in situ by combining lithium hydroxide with acetone cyanohydrin. Then the mechanisms for racemization and the side reaction until the cyanation step were clarified, and these problems were solved. The main features of this process are crystallization of the amide intermediate, since its optical purity is readily improved by recrystallization up to 100% ee in addition to formation of the dibenzylamine salt with ONO-2506 that leads to improved chemical and optical purity of the final product The shorter synthesis, including a one-pot reaction was ruled out because of the hazardous nature of the Katriztky hydrolysis conditions for the conversion of nitrile to amide in the presence of sodium cyanide.
