A kind of synthetic method of tazobactamic acid
A technology for tazobactam acid and a synthesis method, which is applied in directions such as organic chemistry, can solve the problems of long synthesis steps, low yield and high production cost of tazobactam acid, and achieves high product purity, simple operation steps, and high reaction efficiency. short step effect
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0047] The synthesis of embodiment 1 compound B
[0048]Put 216.30g of water, 216.30g of acetone, and 21.63g (0.10mol) of 6-APA into a 1000mL four-necked bottle, cool the above reaction system to -20~-10°C, add 50g of hydrochloric acid with a mass fraction of 36%, dropwise Aqueous hypophosphorous acid solution (26.4g, 0.20mol) with a mass fraction of 50% was added dropwise, and then an aqueous solution of sodium nitrite (46.0g, 0.20mol) with a mass fraction of 30% was added dropwise. - When the residual APA is less than 1%, the reaction is terminated to obtain the compound A reaction solution.
[0049] Heat the above reaction solution to 10-20°C, add 54g NaCl, stir to dissolve, extract 4 times with dimethyl carbonate (108.15g / time), combine dimethyl carbonate layers, add Ce(OTf) 4 (2.21g, 0.003mol), stirred and cooled to 0-10°C, took about 1-2h to add 50% hydrogen peroxide (20.41g, 0.30mol) dropwise, after dropping, raised the temperature to 20-30°C for 5h, and detected the c...
Embodiment 2
[0051] The synthesis of embodiment 2 compound C
[0052] Install a serpentine condenser tube on the 500mL four-necked bottle, and install a vacuum tube connected to a vacuum pump and a valve for adjusting the pumping volume on the upper part of the serpentine condenser tube. Put acetic anhydride (217.24g), compound B (21.72g, 0.1mol) and trifluoroacetic anhydride (1.09g) into the four-neck bottle, adjust the air extraction volume, control the internal temperature to 95-105°C, and reflux under reduced pressure for 8h , HPLC detected that the residual compound B was less than 2%. After the reaction was completed, distilled to dryness under reduced pressure, added isopropanol (217.24g), stirred at 20-25°C for 2h, then cooled to 0-5°C and stirred for 2h, suction filtered, and The obtained filter cake was vacuum-dried at 40-50° C. for 10 h to obtain 21.51 g of compound C with a molar yield of 82.96% and an HPLC purity of 96.15%.
Embodiment 3
[0053] The synthesis of embodiment 3 compound D
[0054] Drop into ethanol (129.65g), dichloromethane (129.65g) and compound C (25.93g, 0.1mol) in the 500mL four-necked bottle, temperature control 35~40 ℃, dropwise add the hydrazine hydrate of industrial grade 80% purity (13.13 g, 0.21mol), the dropping time is about 1h, the dropping is completed, the temperature is controlled at 35-40°C for 5h, and the residual compound C is less than 1% as monitored by HPLC. Water (129.65g), stirred and washed for 20min, the organic layer was separated, the aqueous layer was extracted twice with dichloromethane (129.65g / time), the organic layers were combined, the organic layer was distilled to dryness under reduced pressure, and methyl tert-butyl ether was added (129.65g), crystallized to obtain 21.65g of compound D, the molar yield was 99.66%, and the HPLC purity was 99.86%.
PUM
| Property | Measurement | Unit |
|---|---|---|
| quality score | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More