Sodium taurocholate synthesis

Yield:145-42-6 95%

Reaction Conditions:

Stage #1:Tau;cholic acid with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline;triethylamine in N,N-dimethyl-formamide at 90; for 2 h;
Stage #2: with sodium hydroxide in methanol at 20; for 1 h;

Steps:

1-9; 1; 2 Preparation of sodium taurocholate
5 L of N,N'-dimethylformamide was added to the reaction vessel and the temperature was raised to 90 ° C.Into cholic acid, stirred until solids are dissolved.0.7 kg of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline, 0.3 kg of triethylamine, 0.36 kg of taurine were added, and the reaction was stirred at 90 ° C for 2 h.After cooling to room temperature, 25 L of methyl t-butyl ether was added to the reaction mixture to precipitate a solid, which was filtered.The obtained solid was dissolved in 5 L of methanol, and 0.07 kg of sodium hydroxide was added and stirred at room temperature for 1 h.25 L of methyl tert-butyl ether was added to the reaction vessel, filtered, and dried under vacuum at 60 ° C to obtain a crude sodium taurocholate. Example 3: In 250ml reaction flask was added 20g sodium taurocholate crude (made, HPLC purity 93.78%, 2.53% maximum single hetero) 60ml and methanol,Heat to 50 ° C to dissolve, add 120 ml of ethyl acetate while hot, cool to 25 ° C and stir to crystallize.Filtration and drying under reduced pressure gave 19 g of sodium taurocholate, the yield was 95%, the HPLC content was 99.71%, and the maximum single-B content was 0.29%.As shown in Fig. 3, the peak with a peak time of 9.77 min is sodium taurocholate, and the peak with a peak time of 11.43 min is impurity B: sodium tauro-sodeoxycholate.

References:

Mei Yaoxing (Nanjing) Pharmaceutical Co., Ltd.;Nanjing Hanxin Pharmaceutical Technology Co., Ltd.;Xu Kui;Liu Pengfei;Xu Yonggang;Chen Song;Zhang Haoning CN109776649, 2019, A Location in patent:Paragraph 0047-0068

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