337-03-1

Basic information

• Product Name: Flugestone
• Synonyms: 9-fluoro-11beta,17-dihydroxyprogesterone;FLUGESTONE;9-alpha-fluoro-11-beta,17-alpha-dihydroxypregn-4-ene-3,20-dione;Flugestona;Flugestonum;FLUOROGESTONE ACETATE AND INTERMEDIATE;11β,17-Dihydroxy-9-fluoropregn-4-ene-3,20-dione;9-Fluoro-11β,17-dihydroxypregn-4-ene-3,20-dione
• CAS NO: 337-03-1
• Molecular Formula: C₂₁H₂₉FO₄
• Molecular Weight: 364.45
• EINECS: 206-412-9
• Mol File: 337-03-1.mol
• Article Data: 1

Chemical Properties

• Melting Point: 275-277 °C
• Boiling Point: 522.422 °C at 760 mmHg
• Flash Point: 269.751 °C
• Appearance: /
• Density: 1.262 g/cm³
• Vapor Pressure: 4.26E-13mmHg at 25°C
• Refractive Index: 1.565
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility: Dioxane (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 12.51±0.70(Predicted)
• CAS DataBase Reference: Flugestone(CAS DataBase Reference)
• NIST Chemistry Reference: Flugestone(337-03-1)
• EPA Substance Registry System: Flugestone(337-03-1)

Safety Data

• Hazardous Substances Data: 337-03-1(Hazardous Substances Data)

Usage

Uses

Flugestone is a progestogen and is used as intravaginal sponges/equine chorionic gonadotropins.

InChI:InChI=1/C21H29FO4/c1-12(23)20(26)9-7-15-16-5-4-13-10-14(24)6-8-18(13,2)21(16,22)17(25)11-19(15,20)3/h10,15-17,25-26H,4-9,11H2,1-3H3/t15-,16-,17-,18-,19-,20-,21?/m0/s1

Synthetic route

21-O-methylsulfonyl-9a-fluorocortisone (382-65-0) → 9-fluoro-11β,17-dihydroxy-pregn-4-ene-3,20-dione (337-03-1)

Conditions	Yield
With sodium dithionite; sodium iodide In ethanol; water at 80 - 85℃; Temperature;	77.8%

9,11β-epoxy-17-hydroxy-9β-pregn-4-ene-3,20-dione (2287-53-8) → 9-fluoro-11β,17-dihydroxy-pregn-4-ene-3,20-dione (337-03-1)

Conditions	Yield
With hydrogen fluoride

9-bromo-11β,17-dihydroxy-pregn-4-ene-3,20-dione (102445-69-2) → 9-fluoro-11β,17-dihydroxy-pregn-4-ene-3,20-dione (337-03-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: ethanol; potassium acetate 2: HF View Scheme

Fludrocortisone (127-31-1) → 9-fluoro-11β,17-dihydroxy-pregn-4-ene-3,20-dione (337-03-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine; p-toluenesulfonyl chloride / dichloromethane; toluene / 40 - 45 °C 2: sodium iodide; sodium dithionite / ethanol; water / 80 - 85 °C View Scheme

9-fluoro-11β,17-dihydroxy-pregn-4-ene-3,20-dione (337-03-1) + acetyl chloride (75-36-5) → fluorogestone acetate (2529-45-5)

Conditions	Yield
With triethylamine In chloroform at 10 - 65℃; Temperature;	97.6%

9-fluoro-11β,17-dihydroxy-pregn-4-ene-3,20-dione (337-03-1) → 9-fluoro-17-hydroxy-pregn-4-ene-3,11,20-trione (426-22-2)

Conditions	Yield
With chromium(VI) oxide; acetic acid

Upstream product

• 2287-53-8 9,11β-epoxy-17-hydroxy-9β-pregn-4-ene-3,20-dione 
• 102445-69-2 9-bromo-11β,17-dihydroxy-pregn-4-ene-3,20-dione 
• 382-65-0 21-O-methylsulfonyl-9a-fluorocortisone 
• 127-31-1 Fludrocortisone 

Downstream Products

• 2529-45-5 fluorogestone acetate 

Relevant articles and documents

Preparation method of flurogestone acetate

The invention discloses a preparation method of flurogestone acetate. The preparation method comprises the following steps: using 9a-cortisone bifluoride as a raw material, dissolving 9a-cortisone bifluoride into an organic solvent, and reacting with acyl chloride under the existence of an acid-binding agent to obtain a 9a-cortisone bifluoride-21-O-ester; then reacting the ester with sodium iodide and a sulfur-containing reducing agent in the organic solvent for deesterification, and synthesizing flugestone; and finally reacting the flugestone with acetylchloride or acetic anhydride in the organic solvent, and synthesizing flurogestone acetate. According to the preparation method, 9a-cortisone bifluoride is used as the raw material, flurogestone acetate is synthesized through three-step reaction of 21-site esterification, then reduction and de-esterification and finally 17-site ethyl esterification, and compared with a traditional synthetic method for using a mold removal object acquired through diosgenin processing as a raw material, the preparation method has the advantages such as wide raw material source, short synthetic route, simple, convenient and environmentally-friendly process, few invested equipment and high product yield, and the production cost in the method is reduced by 25% to 30% as compared with a traditional method; and a solvent used in the production can be recycled and circularly used, and is easy for industrial production.