14107-37-0

Basic information

• Product Name: alfadolone
• Synonyms: alfadolone;Pregnane-11,20-dione, 3,21-dihydroxy-, (3.alpha.,5.alpha.)-;(3α,5α)-3,21-Dihydroxypregnane-11,20-dione
• CAS NO: 14107-37-0
• Molecular Formula: C₂₁H₃₂O₄
• Molecular Weight: 348.4764
• EINECS: 237-961-2
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Steroids;Pharmaceuticals, Intermediates & Fine Chemicals, Steroids
• Mol File: 14107-37-0.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 508.5°Cat760mmHg
• Flash Point: 275.4°C
• Appearance: /
• Density: 1.175g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.549
• Storage Temp.: Hygroscopic, Refrigerator, under inert atmosphere
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• CAS DataBase Reference: alfadolone(CAS DataBase Reference)
• NIST Chemistry Reference: alfadolone(14107-37-0)
• EPA Substance Registry System: alfadolone(14107-37-0)

Safety Data

• Hazardous Substances Data: 14107-37-0(Hazardous Substances Data)

Usage

Description

Alfadolone, also known as Alphadolone, is a neuroactive steroid that possesses hypnotic effects. It is one of the key components of the anesthetic drug Althesin, which is used in the medical field for its sedative and hypnotic properties.

Uses

Used in Pharmaceutical Industry:
Alfadolone is used as a sedative and hypnotic agent for its ability to induce sleep and reduce anxiety in patients. It is particularly useful in medical procedures where a calm and relaxed state is required for the patient's comfort and to facilitate the process.
Used in Anesthesia:
Alfadolone is used as a component in the anesthetic drug Althesin, which is administered to patients undergoing surgery or medical procedures that require a deep state of relaxation and sedation. Its hypnotic effects help to ensure a smooth and comfortable experience for the patient while also providing the necessary conditions for the medical team to perform their tasks effectively.

Originator

Alphadolone ,RiboTargets Ltd.

Manufacturing Process

A solution of 3β-acetoxy-5α-pregn-16-ene-11,20-dione (Chamberlin et al., J.Amer. Chem Soc., 1951, 73, 2396) (25.7 g) in dioxan (Analar, 500 ml) was treated with potassium hydroxide (10 g) and water 250 ml and the mixture allowed to stand at room temperature for 1 h. After a further 1 h at 40°C the mixture was diluted with water and the product filtered off. The crude material was dissolved in chloroform and filtered through a column of grade III neutral alumina (100 g). The material obtained was crystallized from acetonepetroleum to give pure 3β-hydroxy-5α-pregn-16-ene-11,20-dione (17.65 g, 77.5%) as small plates, melting point 217.5°C. A solution of 3β-hydroxy-5α-pregn-16-ene-11,20-dione (39.6 g) in dry pyridine (165 ml) was treated with toluene-p-sulfonyl chloride (43.9 g) to give the toluene sulfonate (56.7 g), melting point 147-151°C. A portion (10.7 g) of this material was crystallized from ethyl acetate-petroleum to give the pure 3β-toluene-p-sulfonyloxy-5α-pregn-16-ene-11,20-dione (9.2 g) as plates, melting point 154°-155°C. 2 Methods of producing of 3α-hydroxy-5α-pregn-16-ene-11,20-dione from 3β- toluene-p-sulfonyloxy-5α-pregn-16-ene-11,20-dione: 1. A solution of 3β-toluene-p-sulfonyloxy-5α-pregn-16-ene-11,20-dione (19.1 g) in N,N-dimethylformamide (160 ml) and water (16.0 ml) was treated with potassium acetate (29.2 g) and the mixture heated at 115°C for 2.5 h. The solvents were removed in vacuo and residue partitioned between chloroform and water. The chloroform extract was washed with water, dried and evaporated. The residue was taken up in methanol (500 ml) and solution flushed with nitrogen. Potassium hydroxide (17 g) in water (70 ml) was added and the solution refluxed for 1 h. Glacial acetic acid was added to bring the pH to about 6 and most of the methanol evaporated in vacuo. Dilution with water gave a gummy precipitate which was extracted into chloroform to give the crude product. This material was extracted with ether and the residue boiled with benzene. The insoluble material was crystallized from chloroformpetroleum to give 3α-hydroxy-5α-pregn-16-ene-11,20-dione (3.28 g) as large prisms, melting point 243°-244°C. 2. A mixture of the 3β-toluene-p-sulfonyloxy-5α-pregn-16-ene-11,20-dione (60 g; 0.124 mole) in N,N-dimethylformamide (350 ml) and potassium acetate (92 g, 0.94 mole) in water (935 ml) was stirred at 115°C for 4 h. The brown solution was cooled and most of the N,N-dimethylformamide removed by evaporation at 50°C and 4 mm to give a brown solid mass. Another run with to sylate (58 g, 0.12 mole), potassium acetate (90 g, 0.91 mole), N,Ndimethylformamide (350 ml) and water (35 ml) was carried out as described above. The combined aqueous fractions were extracted with chloroform (3 x 100 ml) and dried over magnesium sulfate. The chloroform was removed in vacuo and residual N,N-dimethylformamide was evaporated at 50°C and 4 mm to give the crude 3α-acetate-5α-pregn-16-ene-11,20-dione (92 g) as a brown solid. A solution of 3α-acetate-5α-pregn-16-ene-11,20-dione (92 g) in dioxin (1000 ml) was mixed with a solution of potassium hydroxide (45 g, 0.8 mole) in water (500 ml) to give a two-phase system. A homogeneous solution was obtained by the addition of dioxin (440 ml) and water (625 ml). Nitrogen was bubbled through the solution which was heated at 50°C for 2 h. The port colored solution was treated with glacial acetic acid (40 ml) to bring the pH about 7 and two thirds of the solvent was removed by distillation in vacuo (water pump). Water (3 L) was added to the resultant mixture (which had already begun to crystallize) and the precipitated solid was filtered off, washed with water and dried over phosphorus pentoxide to give the crude 3α- hydroxy-5α-pregn-16-ene-11,20-dione (73.9 g). Producing of 3α,21-dihydroxy-5α-pregnane-11,20-dione from 3α-hydroxy-5α- pregn-16-ene-11,20-dione: A solution of 3α-hydroxy-5α-pregn-16-ene-11,20-dione (200 mg) in freshly distilled tetrahydrofuran (8 ml) with 5% palladium on carbon (100 mg) was hydrogenated till hydrogen uptake ceased. The mixture was filtered through a pad of kieselguhr and the tetrahydrofuran removed in vacuo to give 3α- hydroxy-5α-pregnane-11,20-dione (196 mg), melting point 171°-172°C. Boron trifluoride etherate (37.9 ml) was added to a stirred solution of 3α- hydroxy-5α-pregnane-11,20-dione (6.64 g, 20 mmol) and lead tetraacetate (10.1 g, 22 mmol) in dry benzene (280 ml) and methanol (15.1 ml) at room temperature. After 2 h the mixture was poured into water (2 L) and extracted with ether (1 L). The combined ether extracts were washed successively with sodium bicarbonate solution and water, dried over magnesium sulfate, and concentrated in vacuo to give a white crystalline mass. Four recrystallizations from acetone-petroleum (b.p. 40°-60°C) gave 21-acetoxy-3α-hydroxy-5α- pregnane-11,20-dione as fine needles (4.22 g, 54%), melting point 172°- 173°C. The 3α,21-dihydroxy-5α-pregnane-11,20-dione is conveniently prepared by the deacylation of 21-acetoxy-3α-hydroxy-5α-pregnane-11,20-dione under basic conditions, for example, in the presence of potassium or sodium hydrogen carbonate, conveniently in the presence of a solvent e.g. methanol, ethanol or tetrahydrofuran, reesterifying the resultant product.

Therapeutic Function

Anesthetic

InChI:InChI=1/C21H32O4/c1-20-8-7-13(23)9-12(20)3-4-14-15-5-6-16(18(25)11-22)21(15,2)10-17(24)19(14)20/h12-16,19,22-23H,3-11H2,1-2H3/t12-,13+,14-,15-,16+,19+,20-,21-/m0/s1

Relevant articles and documents

Chemical compounds

Steroids of the androstane series having a 3α-hydroxy group, a 3β-hydrogen or methyl group; a 10-hydrogen atom or methyl group, an 11-oxo group or two hydrogen atoms at the 11-position, a 17α-hydrogen atom, and a group at the 17β-position which is esterified carboxyl group, an N-mono or di-substituted carbamoyl group, a cyano group, a formyl group or an acetalised formyl group; and the 3α-esters thereof. The steroids possess anaesthetic properties.