27262-47-1Relevant articles and documents
Preparation method of bupivacaine and intermediate (S)-2-piperidinecarboxylic acid thereof
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Paragraph 0025; 0077-0081, (2021/06/13)
The invention discloses bupivacaine and a preparation method of an intermediate (S)-2-piperidinecarboxylic acid of the bupivacaine; wherein the intermediate (S)-2-piperidinecarboxylic acid is prepared by taking (R)-4-benzyl-2-oxazolidinone as a chiral auxiliary agent through amidation, asymmetric alkylation, hydrolysis, cyclization and auxiliary group removal; wherein the prepared (S)-2-piperidinecarboxylic acid is used as a raw material to prepare the local anesthetic (S)-bupivacaine. The method utilizes cheap and easily available organic raw materials, and has the advantages of simple operation, mild reaction conditions, good stereoselectivity, high yield and the like.
Levobupivacaine intermediate compound
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Paragraph 0032; 0072-0097, (2021/07/10)
The invention belongs to the technical field of medicine synthesis, and particularly relates to a levobupivacaine intermediate compound. The preparation method comprises the following steps: reacting 2-chloropiperidine containing S configuration with n-butyl bromide to generate a novel intermediate compound IV containing S configuration. The novel levobupivacaine intermediate compound IV provided by the invention does not generate larger impurities in the subsequent substitution reaction for preparing levobupivacaine, the levobupivacaine obtained by utilizing the novel intermediate avoids condensation of traditional carboxyl and amido and avoids resolution, and the obtained product is also higher in purity.
Enantioseparation of racemic bupivacaine via ultrasonic-assisted diastereomeric crystallization using 12,14-dinitrodehydroabietic acid
Ge, Li,Zhu, Yi,Qi, Yonghui,Chen, Yande,Yang, Kedi
, p. 256 - 261 (2019/02/05)
12,14-Dinitrodehydroabietic acid (12,14-dinitroDHAA), a chiral acid obtained by the nitration of optical dehydroabietic acid (DHAA), was successfully employed as resolving agent. The resolution of racemic bupivacaine by ultrasonic-assisted diastereomeric crystallization in ethanol was investigated. The results indicated that ultrasonic-assist can well facilitate resolution of (R,S)-bupivacaine and a higher enantiomeric excess (ee) and yield was obtained for (S)-bupivacaine, and while without ultrasound, the ee value decreases by increasing the crystallization time. A Box-Behnken experimental design with four factors (amount of 12,14-dinitroDHAA, ethanol amount, ultrasonic power and crystallization temperature) combined with response surface methodology (RSM) was applied to explore resolution effects. A second-order polynomial equation was adequate to model the relationship between the ee (or yield) and the dependent variables. When maintaining a lower limit of 90% for the yield of (S)-bupivacaine, the optimal resolution conditions by RSM were 12,14-dinitroDHAA/bupivacaine molar ratio of 1.6, solvent/propranolol ratio of 16.5 mL/g, 63.2 W ultrasonic power and crystallization temperature of 0 °C, respectively. Under the optimal conditions, the experimental ee and yield of (S)-bupivacaine were 69.8% and 87.5%.