ChemicalBook CAS DataBase List Spironolactone

Spironolactone synthesis

12synthesis methods

Product Name:Spironolactone
CAS Number:52-01-7
Molecular formula:C24H32O4S
Molecular Weight:416.58

Spironolactone is the 7-acetate of the γ-lactone of 17-hydroxy-7-mercapto- 3-oxo-17-α-pregn-4-ene-21-carboxylic acid (21.5.8). Spironolactone is synthesized industrially in two different ways from androstenolone—3β-hydroxy-5-androsten-17-one. According to the first method, androstenolone undergoes ethynylation by acetylene in a Normant reaction condition using sodium amide in liquid ammonia, which forms 17 α-ethynyl-3β-,17β-dihydroxy-5-androstene (21.5.1). Subsequent reaction of this with methylmagnesiumbromide and then with carbon dioxide gives the corresponding propenal acid (21.5.2). Reduction of the triple bond in this product with hydrogen using a palladium on calcium carbonate catalyst forms the corresponding acrylic acid derivative (21.5.3), which is treated with acid without being isolated, which leads to cyclization into an unsaturated lactone derivative (21.5.4). The double bond is reduced by hydrogen, in this case using a palladium on carbon catalyst. The resulting lactone 21.5.5 undergoes oxidation in an Oppenauer reaction, giving an unsaturated keto-derivative—4-androsten-3,17-dione (21.5.6). Further oxidation of the product (21.5.6) using chloroanyl gives dienone (21.5.7), which when reacted with thioacetic acid gives the desired spionolactone (21.5.8).

976-71-6
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507-09-5
314 suppliers
$12.00/5g

52-01-7
483 suppliers
$17.00/1mg

Yield:52-01-7 76%

Reaction Conditions:

Stage #1: tiolacetic acidwith trifluoromethylsulfonic anhydride in tetrahydrofuran;
Stage #2: canrenone in tetrahydrofuran at 20; for 1 h;

Steps:

5 Example 5 Synthesis of Spiro Lactone of Compound of Formula (I)

20 mmol of freshly distilled thioacetic acid, 20 mmol of trimethylsilyl triflate and 100 mL of tetrahydrofuran were added to the reaction flask. After stirring well, 10 mmol of the compound of formula (IV) was added and the reaction was stirred at room temperature for 1 h.Then, 50 mL of ethyl acetate was added to the reaction flask,Then slowly add 50mL saturated sodium carbonate solution, stirred at room temperature for 0.5h,The reaction solution was then extracted with 50 mL of ethyl acetate in three portions, and the organic layers were combined.Drying over anhydrous sodium sulfate and evaporation of the solvent under reduced pressure gave a light brown solid,Recrystallization from methanol gave crystals of the white compound of formula (I). Yield:76%, by HPLC normalized purity: 99.6%.

References:

CN107312060,2017,A Location in patent:Paragraph 0031; 0032

976-71-6
257 suppliers
$33.00/25mg

507-09-5
314 suppliers
$12.00/5g