981-34-0

Basic information

• Product Name: 9beta,11beta-Epoxy-17alpha,21-dihydroxy-16beta-methylene-pregna-1,4-diene-3,20-dione
• Synonyms: 16-BETA METHYL EPOXIDE;9beta,11beta-epoxy-17alpha,21-dihydroxy-16beta-methylene-pregna-1,4-diene-3,20-dione;DB11;(9β)-9,11β-Epoxy-16β-methyl-17,21-dihydroxypregna-1,4-diene-3,20-dione;9β,11β-Epoxy-17,21-dihydroxy-16β-methylpregna-1,4-diene-3,20-dione;Einecs 213-563-4;Betamethasone 9,11-Epoxide;9beta,11beta-Epoxy-1
• CAS NO: 981-34-0
• Molecular Formula: C₂₂H₂₈O₅
• Molecular Weight: 370.44
• EINECS: 213-563-4
• Product Categories: Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Steroids
• Mol File: 981-34-0.mol
• Article Data: 4

Chemical Properties

• Melting Point: 210-220 ºC
• Boiling Point: 564.9 °C at 760 mmHg
• Flash Point: 198.1 °C
• Appearance: off-white solid
• Density: 1.32 g/cm³
• Vapor Pressure: 4.09E-15mmHg at 25°C
• Refractive Index: 1.616
• Storage Temp.: Refrigerator
• PKA: 12.56±0.70(Predicted)
• CAS DataBase Reference: 9beta,11beta-Epoxy-17alpha,21-dihydroxy-16beta-methylene-pregna-1,4-diene-3,20-dione(CAS DataBase Reference)
• NIST Chemistry Reference: 9beta,11beta-Epoxy-17alpha,21-dihydroxy-16beta-methylene-pregna-1,4-diene-3,20-dione(981-34-0)
• EPA Substance Registry System: 9beta,11beta-Epoxy-17alpha,21-dihydroxy-16beta-methylene-pregna-1,4-diene-3,20-dione(981-34-0)

Safety Data

• Hazardous Substances Data: 981-34-0(Hazardous Substances Data)

Usage

Description

9beta,11beta-Epoxy-17alpha,21-dihydroxy-16beta-methylene-pregna-1,4-diene-3,20-dione is a complex organic compound belonging to the steroid family. It is characterized by its unique molecular structure, featuring an epoxy group at the 9beta and 11beta positions, hydroxy groups at the 17alpha and 21 positions, and a methylene group at the 16beta position. This off-white solid has low solubility in most solvents, making it a challenging compound to work with in various applications.

Uses

Used in Pharmaceutical Industry:
9beta,11beta-Epoxy-17alpha,21-dihydroxy-16beta-methylene-pregna-1,4-diene-3,20-dione is used as a metabolite in the pharmaceutical industry for two specific applications. First, it serves as a metabolite of Beclometasone, a potent corticosteroid medication used for treating various inflammatory conditions, such as asthma, allergies, and skin disorders. Second, it is also a metabolite of Mometasone furoate, another corticosteroid medication used for treating nasal and respiratory conditions, including allergic rhinitis and chronic obstructive pulmonary disease (COPD).
The role of 9beta,11beta-Epoxy-17alpha,21-dihydroxy-16beta-methylene-pregna-1,4-diene-3,20-dione as a metabolite in these medications is crucial, as it helps in understanding the metabolic pathways and pharmacokinetics of the drugs, ultimately contributing to their safety and efficacy profiles.

InChI:InChI=1/C22H28O5/c1-12-8-16-15-5-4-13-9-14(24)6-7-19(13,2)22(15)18(27-22)10-20(16,3)21(12,26)17(25)11-23/h6-7,9,12,15-16,18,23,26H,4-5,8,10-11H2,1-3H3/t12-,15-,16-,18-,19-,20-,21-,22+/m0/s1

Synthetic route

21-acetoxy-17α-hydroxy-9β,11β-epoxy-16β-methylpregna-4-ene-3,20-dione → 17α,21-dihydroxy-9β,11β-epoxy-16β-methylpregna-1,4-diene-3,20-dione (981-34-0)

Conditions	Yield
With D-Glucose In aq. phosphate buffer for 76h; Microbiological reaction;	83%

C25H33BrO7 → 17α,21-dihydroxy-9β,11β-epoxy-16β-methylpregna-1,4-diene-3,20-dione (981-34-0)

Conditions	Yield
In dichloromethane; water at 25 - 30℃; for 1h; Inert atmosphere;	75%
With sodium hydroxide In methanol; dichloromethane at 0 - 5℃;

Carbonic acid 2-((8S,9S,10R,11R,13S,14S,16S,17R)-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl)-2-oxo-ethyl ester ethyl ester → 17α,21-dihydroxy-9β,11β-epoxy-16β-methylpregna-1,4-diene-3,20-dione (981-34-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: phosphorus pentachloride / tetrahydrofuran / 1 h / -85 °C 2: perchloric acid; 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione / water / 0.25 h / 10 - 20 °C 3: sodium hydroxide / dichloromethane; water; methanol / 3 h / -5 - 0 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: phosphorus pentachloride / tetrahydrofuran / 1 h / -85 °C 2: perchloric acid; 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione / water; N,N-dimethyl-formamide / 1 h / 20 °C 3: sodium hydroxide / dichloromethane; methanol / 0 - 5 °C View Scheme
Multi-step reaction with 4 steps 1: phosphorus pentachloride; pyridine / dichloromethane / 0.75 h / 20 °C 2: dimethyl sulfoxide / 3 h / 90 °C 3: perchloric acid; 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione / water / 0.25 h / 10 - 20 °C 4: sodium hydroxide / dichloromethane; water; methanol / 3 h / -5 - 0 °C / Inert atmosphere View Scheme

C26H36O9S → 17α,21-dihydroxy-9β,11β-epoxy-16β-methylpregna-1,4-diene-3,20-dione (981-34-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium acetate; acetic acid / 115 °C 2: perchloric acid; 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione / water / 0.25 h / 10 - 20 °C 3: sodium hydroxide / dichloromethane; water; methanol / 3 h / -5 - 0 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: sodium acetate; acetic acid / 115 °C 2: perchloric acid; 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione / water; N,N-dimethyl-formamide / 1 h / 20 °C 3: sodium hydroxide / dichloromethane; methanol / 0 - 5 °C View Scheme

C26H33BrO8 → 17α,21-dihydroxy-9β,11β-epoxy-16β-methylpregna-1,4-diene-3,20-dione (981-34-0)

Conditions	Yield
With sodium hydroxide In methanol; dichloromethane; water at -5 - 0℃; for 3h; Inert atmosphere;

17α-hydroxy-16β-methyl-21-ethoxycarbonyloxypregna-1,4,9(11)-triene-3,20-dione (56665-79-3) → 17α,21-dihydroxy-9β,11β-epoxy-16β-methylpregna-1,4-diene-3,20-dione (981-34-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: perchloric acid; 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione / water; N,N-dimethyl-formamide / 1 h / 20 °C 2: sodium hydroxide / dichloromethane; methanol / 0 - 5 °C View Scheme

21-Chloro-17α-hydroxy-16β-methylpregna-1,4,9(11)-triene-3,20-dione (116846-77-6) → 17α,21-dihydroxy-9β,11β-epoxy-16β-methylpregna-1,4-diene-3,20-dione (981-34-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium iodide / N,N-dimethyl-formamide / 3 h / 60 °C 2: perchloric acid; 5,5-dibromohydantoin / water / 3 h / -5 °C 3: sodium sulfite; sodium hydroxide / water; methanol / 3 h / 10 °C View Scheme

Acetic acid 2-((8S,9R,10S,11S,13S,14S,16S,17R)-9-bromo-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl)-2-oxo-ethyl ester → 17α,21-dihydroxy-9β,11β-epoxy-16β-methylpregna-1,4-diene-3,20-dione (981-34-0)

Conditions	Yield
With sodium hydroxide; sodium sulfite In methanol; water at 10℃; for 3h;

17α,21-dihydroxy-9β,11β-epoxy-16β-methylpregna-1,4-diene-3,20-dione (981-34-0) → betamethasone (378-44-9)

Conditions	Yield
With hydrogen fluoride In water; N,N-dimethyl-formamide at -15℃;	89%
With hydrogen fluoride

17α,21-dihydroxy-9β,11β-epoxy-16β-methylpregna-1,4-diene-3,20-dione (981-34-0) → 9β,11β-epoxy-16β-methylandrosta-1,4-diene-3,17-dione (1192715-48-2)

Conditions	Yield
With bithmuth(III) triflate hydrate In 1,4-dioxane at 80℃; chemoselective reaction;	45%

17α,21-dihydroxy-9β,11β-epoxy-16β-methylpregna-1,4-diene-3,20-dione (981-34-0) → dexamethasone (50-02-2)

Conditions	Yield
With hydrogen fluoride

Upstream product

• 116846-77-6 21-Chloro-17α-hydroxy-16β-methylpregna-1,4,9(11)-triene-3,20-dione 
• 1035-69-4 androst-4,9⁽¹¹⁾-dien-3,17-dione 
• 56665-79-3 17α-hydroxy-16β-methyl-21-ethoxycarbonyloxypregna-1,4,9(11)-triene-3,20-dione 
• 85650-69-7 C₂₆H₃₆O₉S 

Downstream Products

• 378-44-9 betamethasone 
• 4419-39-0 beclomethasone 
• 5534-18-9 beclomethasone 17-monopropionate 
• 5534-09-8 beclomethasone 17,21-dipropionate 
• 205105-83-5 (9β,11β,16β)-9,11-epoxy-17-hydroxy-16-methyl-21-(1-oxopropoxy)pregna-1,4-diene-3,20-dione 
• 50-02-2 dexamethasone 

Relevant articles and documents

Preparation method of betamethasone epoxide

The invention provides a preparation method of a betamethasone epoxide, which comprises the steps of step 1, preparing a first reaction solution containing a compound II by using a compound I based onan esterification reaction; step 2, based on a bromine hydroxylation reaction, preparing a second reaction solution containing a compound III by using the first reaction solution; and 3, based on a hydrolysis reaction, preparing a betamethasone epoxide IV crude product by using the second reaction solution. The betamethasone epoxide IV is synthesized from the compound I by adopting a one-pot method, the method has the advantages of high yield, simplicity and safety in operation, low cost, small pollution and the like, and the method is stable and easy to realize industrial production.

A betamethasone ring oxygen water peptide synthesis method

The invention belongs to the field of steroid hormone drug synthesis, and particularly relates to a synthesis method of a betamethasone epoxy hydrolyzate, which comprises the following step: by using a betamethasone suppressor as a raw material, carrying out bromohydroxylation reaction and epoxy hydrolysis reaction to obtain the betamethasone epoxy hydrolyzate finished product, thereby enhancing the overall yield of the betamethasone epoxy hydrolyzate by reducing the elutriation running. The method reduces the hydrolysis of the bromohydroxy substance in the reaction, and integrates the steps of epoxidation and hydrolysis into one step, thereby enhancing the yield of the betamethasone epoxy hydrolyzate.