Development of a packed-bed flow process for the production scale hydrogenation of 7-oxo-lithocholic acid to ursodeoxycholic acid
- Seung Jae Lee1, 2
- Yashwardhan R. Malpani2
- Il Won Kim1
- 1Department of Chemical Engineering, Soongsil University, 369 Sangdo-ro, Dongjak-gu 06978 Seoul, Republic of Korea
- 2API Synthesis Team, Daewoong-Bio, 29-Jeyakdanji-ro, Hyangnam-eup, Hwaseung-si, Gyeonggi-do 18608, Republic of KoreaRead the publication that featured this abstract
A continuous flow process for the synthesis of ursodeoxycholic acid (UDCA) from 7-oxo-lithocholic acid (7-oxo-LCA) through catalytic hydrogenation was developed from the lab scale to the final production scale. Various parameters, such as catalyst, solvent, base equivalence, feed flow rate, temperature, and pressure, were optimized under the flow conditions suitable for the final production in the pilot and production scale. Heterogeneous Raney-Ni catalyst was optimal in terms of conversion ratio and stereoselectivity when solvent and base equivalence were 2-propanol and > 1.5, respectively. It was employed under the packed-bed flow conditions with hydrogen gas. The scale-up was carried out up to 155 kg lot production scale. The developed process has an advantage over the widely used alkali metal reduction of 7-oxo-LCA to UDCA being more convenient and safer. Also, it produces UDCA with high stereoselectivity (> 23) and a fast production rate (> 4 kg/h). The synthesized product is suitable for the recrystallization to generate a high purity UDCA (> 99.5%) in a sufficient isolation yield (ca. 70%). Overall a production scale continuous process for UDCA was realized in a highly efficient manner.
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