Prednicarbate

White or almost white, crystalline powder.

Solid

With prednisolone as the raw material. 110g (0.305mol) of prednisolone was dissolved in 2.2L of anhydrous dioxane, and 147ml (0.70mol) of tetraethyl orthocarbonate and 12g of p-toluenesulfonic acid were added. Stir or place at 22°C for 17h. The reaction solution was poured into 17L of water and neutralized with sodium bicarbonate. Firstly, an oily substance precipitated out and formed crystals after being left for 1 to 24 hours. Filter and wash. In the presence of phosphorus pentoxide, it was dried under high vacuum to constant weight to obtain 126.5g of compound (I) with a yield of 90%. Recrystallization from dichloromethane-ethanol-ether gave compound (I) which could be used for analysis, melting point 155°C. 125g (0.27mol) of compound (I) was dissolved in 1.4L of anhydrous acetic acid, and under stirring at 18°C, 10ml of water was added. After standing at 18°C ​​for 5h, it was stirred with 18L of water containing 1kg of sodium chloride. The precipitate was collected by filtration and washed with water. In the presence of phosphorus pentoxide, dry under high vacuum to constant weight to obtain 72g of crude product. The filtrate was concentrated under reduced pressure, and a solid precipitated out again, and 36 g was obtained after drying. A total of 108g of the crude product of Compound (II) was obtained with a yield of 92.3%. After the crude product is recrystallized from acid-free dichloromethane-ethanol, it can be used in the next reaction. Standards used for analysis can be chromatographed on silica gel, eluted with anhydrous dichloromethane, to obtain high-quality products, melting point 145 ℃. There are two methods for obtaining prednisate from compound (II). Method 1: 68.5g (0.158mo1) of compound (II) was dissolved in 680ml of anhydrous pyridine. Under stirring at 0°C, 18.2g (0.197mo1) of propionyl chloride was added dropwise within 60min. After stirring at 0 °C for 30 min, it was stirred at 20 °C for 2 h. The reaction solution was poured into 18 L of water containing 1 kg of sodium chloride. The precipitate was collected by filtration and washed thoroughly with water. In the presence of phosphorus pentoxide, it was dried under high vacuum to constant weight to obtain 63g of crude prednisate, with a yield of 81.4%. 10g of this crude product was chromatographed on 200g of silica gel, eluting with toluene-ethyl acetate. After concentration, it was recrystallized with ethanol-ether to obtain 5.7g of prednisate, with a yield of 57% and a melting point of 110-112°C. 4g of the fine product was heated in 80ml of isopropyl ether for 60min, filtered, and dried to obtain crystals with higher melting point, melting point 183℃. Method 2: 1.05kg (2.43mol) of the crude compound (II) was dissolved in 10L of anhydrous dichloromethane and 0.336I was added dropwise at 20°C. (2.6mol) Propionic anhydride, then add 50g (0.41mol) 4-dimethylaminopyridine. After stirring at 20°C for 16h, the reaction solution was washed successively with water, aqueous sodium bicarbonate solution and water, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was similar to the above method. After chromatography, it was recrystallized with isopropyl ether to obtain 360 g of crude prednisate, with a yield of 30.4% and a melting point of 110 to 112°C.

Topical anti-inflammatory agent. Glucocorticoid.

Molecular Weight:488.6
XLogP3:4.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:8
Rotatable Bond Count:9
Exact Mass:488.24101810
Monoisotopic Mass:488.24101810
Topological Polar Surface Area:116
Heavy Atom Count:35
Complexity:982
Undefined Atom Stereocenter Count:7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes