58652-20-3

Basic information

• Product Name: Nomegestrol 17-acetate
• Synonyms: 19-Norpregna-4,6-diene-3,20-dione,17-(acetyloxy)-6-Methyl-;17-Acetoxy-6-methyl-19-norpregna-4,6-diene-3,20-dione;Org 10486-0;Nomegestrol Acetate-d3;MELEGESTROL ACETATE;17-hydroxy-6-methyl-19-norpregna-4,6-diene-3,20-dione 17-acetate;17ALPHA-ACETOXY-6ALPHA-METHYL-19-NOR-PREGN-4,6-DIEN-3,20-DIONE;nomegestrol 17-acetate
• CAS NO: 58652-20-3
• Molecular Formula: C₂₃H₃₀O₄
• Molecular Weight: 370.48
• EINECS: 261-379-8
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Steroids
• Mol File: 58652-20-3.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 507.3 °C at 760 mmHg
• Flash Point: 219.8 °C
• Appearance: white to tan/
• Density: 1.16 g/cm³
• Vapor Pressure: 2.06E-10mmHg at 25°C
• Refractive Index: 1.554
• Storage Temp.: 2-8°C
• Solubility: DMSO: ≥7mg/mL
• CAS DataBase Reference: Nomegestrol 17-acetate(CAS DataBase Reference)
• NIST Chemistry Reference: Nomegestrol 17-acetate(58652-20-3)
• EPA Substance Registry System: Nomegestrol 17-acetate(58652-20-3)

Safety Data

• Hazard Codes: N
• Statements: 63-50
• Safety Statements: 61
• RIDADR: UN 3077 9 / PGIII
• WGK Germany: 3
• RTECS: RC8899200
• Hazardous Substances Data: 58652-20-3(Hazardous Substances Data)

Usage

Description

Nomegestrol 17-acetate is a synthetic progestin, a derivative of the naturally occurring hormone progesterone. It is characterized by its white or almost white, crystalline powder form and is known for its role in various medical applications, particularly in hormone replacement therapies and contraception.

Uses

Used in Hormone Replacement Therapy:
Nomegestrol 17-acetate is used as a progesterone substitute in implantable hormone replacement therapies. It helps to alleviate symptoms associated with hormonal imbalances, such as those experienced during menopause or in cases of certain medical conditions.
Used in Contraception:
Nomegestrol 17-acetate is also utilized as a contraceptive agent, where it works to prevent ovulation and thus, the possibility of pregnancy. Its progestin properties make it an effective component in various contraceptive formulations, including oral contraceptives and implantable devices.

InChI:InChI=1/C23H30O4/c1-13-11-20-18(17-6-5-16(26)12-19(13)17)7-9-22(4)21(20)8-10-23(22,14(2)24)27-15(3)25/h11-12,17-18,20-21H,5-10H2,1-4H3/t17-,18-,20-,21+,22+,23+/m1/s1

Synthetic route

17α-acetoxy-6-methylene-19-norpregn-4-ene-3,20-dione (58652-19-0) → nomegestrol acetate (58652-20-3)

Conditions	Yield
With [Rh(Binap)2]+[ClO4]- In tetrahydrofuran at 80℃; for 0.5h; Solvent; Temperature; Sealed tube; Inert atmosphere;	99%
With palladium 10% on activated carbon; acetic acid In ethanol at 72 - 75℃; for 0.166667h; Temperature; Inert atmosphere; Large scale;	90.2%
With 5%-palladium/activated carbon In tetrahydrofuran; ethanol for 0.75h; Reflux;	77%

C23H32O4 → nomegestrol acetate (58652-20-3)

Conditions	Yield
With chloranil In 1,4-dioxane at 90 - 95℃; Solvent; Temperature;	77.8%

17α-hydroxy-3-methoxy-19-norpregna-1,3,5(10)-trien-20-one (1624-58-4) → nomegestrol acetate (58652-20-3)

Conditions

Yield

Multi-step reaction with 8 steps 1: toluene-4-sulfonic acid; trimethyl orthoformate / dichloromethane / 2 h / 20 °C 2: sodium; ammonia / ethanol; water; tetrahydrofuran; tert-butyl alcohol / -60 °C / Inert atmosphere 3: hydrogenchloride / water; tetrahydrofuran / 0.33 h / 60 °C 4: toluene-4-sulfonic acid / 24 h / 20 °C 5: toluene-4-sulfonic acid / tetrahydrofuran / 24 h / 20 °C 6: trichlorophosphate / -10 °C 7: sodium tetrahydroborate / methanol / 20 °C 8: 5%-palladium/activated carbon / ethanol; tetrahydrofuran / 0.75 h / Reflux View Scheme

20,20-(ethylenedioxy)-3-methoxy-17α-hydroxy-19-norpregna-1,3,5(10)-triene (14328-46-2) → nomegestrol acetate (58652-20-3)

Conditions

Yield

Multi-step reaction with 7 steps 1: sodium; ammonia / ethanol; water; tetrahydrofuran; tert-butyl alcohol / -60 °C / Inert atmosphere 2: hydrogenchloride / water; tetrahydrofuran / 0.33 h / 60 °C 3: toluene-4-sulfonic acid / 24 h / 20 °C 4: toluene-4-sulfonic acid / tetrahydrofuran / 24 h / 20 °C 5: trichlorophosphate / -10 °C 6: sodium tetrahydroborate / methanol / 20 °C 7: 5%-palladium/activated carbon / ethanol; tetrahydrofuran / 0.75 h / Reflux View Scheme

17-alpha-Hydroxy-19-norprogesterone (2137-18-0) → nomegestrol acetate (58652-20-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: toluene-4-sulfonic acid / 24 h / 20 °C 2: toluene-4-sulfonic acid / tetrahydrofuran / 24 h / 20 °C 3: trichlorophosphate / -10 °C 4: sodium tetrahydroborate / methanol / 20 °C 5: 5%-palladium/activated carbon / ethanol; tetrahydrofuran / 0.75 h / Reflux View Scheme

Estrone (53-16-7) → nomegestrol acetate (58652-20-3)

Conditions

Yield

Multi-step reaction with 12 steps 1.1: sodium hydroxide / acetone; water / 2 h / Reflux 2.1: potassium tert-butylate / tetrahydrofuran / 0 - 20 °C 3.1: triethylamine / dichloromethane / 2 h / 0 - 20 °C 4.1: sodium methylate / methanol / Reflux 4.2: 2 h / Reflux 5.1: toluene-4-sulfonic acid; trimethyl orthoformate / dichloromethane / 2 h / 20 °C 6.1: sodium; ammonia / ethanol; water; tetrahydrofuran; tert-butyl alcohol / -60 °C / Inert atmosphere 7.1: hydrogenchloride / water; tetrahydrofuran / 0.33 h / 60 °C 8.1: toluene-4-sulfonic acid / 24 h / 20 °C 9.1: toluene-4-sulfonic acid / tetrahydrofuran / 24 h / 20 °C 10.1: trichlorophosphate / -10 °C 11.1: sodium tetrahydroborate / methanol / 20 °C 12.1: 5%-palladium/activated carbon / ethanol; tetrahydrofuran / 0.75 h / Reflux View Scheme

17α-acetoxy-19-norpregna-4-ene-3,20-dione (31981-44-9) → nomegestrol acetate (58652-20-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: toluene-4-sulfonic acid / tetrahydrofuran / 24 h / 20 °C 2: trichlorophosphate / -10 °C 3: sodium tetrahydroborate / methanol / 20 °C 4: 5%-palladium/activated carbon / ethanol; tetrahydrofuran / 0.75 h / Reflux View Scheme
Multi-step reaction with 4 steps 1: orthoformic acid triethyl ester; toluene-4-sulfonic acid / dichloromethane / 25 - 30 °C 2: sodium hydroxide; dihydrogen peroxide / methanol / 20 - 25 °C 3: magnesium / chloroform; diethyl ether / 30 - 55 °C 4: chloranil / 1,4-dioxane / 90 - 95 °C View Scheme
Multi-step reaction with 4 steps 1: orthoformic acid triethyl ester; toluene-4-sulfonic acid / dichloromethane / 25 - 30 °C 2: sodium hydroxide; dihydrogen peroxide / methanol / 20 - 25 °C 3: magnesium / tetrahydrofuran / 30 - 55 °C 4: chloranil / 1,4-dioxane / 90 - 95 °C View Scheme
Multi-step reaction with 4 steps 1: orthoformic acid triethyl ester; toluene-4-sulfonic acid / dichloromethane / 25 - 30 °C 2: sodium hydroxide; dihydrogen peroxide / methanol / 20 - 25 °C 3: magnesium / toluene / 30 - 55 °C 4: chloranil / 1,4-dioxane / 90 - 95 °C View Scheme

3-ethoxy-17α-acetoxy-19-norpregna-3,5-diene-20-one → nomegestrol acetate (58652-20-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: trichlorophosphate / -10 °C 2: sodium tetrahydroborate / methanol / 20 °C 3: 5%-palladium/activated carbon / ethanol; tetrahydrofuran / 0.75 h / Reflux View Scheme

6-formyl-3-ethoxy-17α-acetoxy-19-norpregna-3,5-diene-20-one (147508-40-5) → nomegestrol acetate (58652-20-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / methanol / 20 °C 2: 5%-palladium/activated carbon / ethanol; tetrahydrofuran / 0.75 h / Reflux View Scheme

estrone 3-methyl ether (1624-62-0) → nomegestrol acetate (58652-20-3)

Conditions

Yield

Multi-step reaction with 11 steps 1.1: potassium tert-butylate / tetrahydrofuran / 0 - 20 °C 2.1: triethylamine / dichloromethane / 2 h / 0 - 20 °C 3.1: sodium methylate / methanol / Reflux 3.2: 2 h / Reflux 4.1: toluene-4-sulfonic acid; trimethyl orthoformate / dichloromethane / 2 h / 20 °C 5.1: sodium; ammonia / ethanol; water; tetrahydrofuran; tert-butyl alcohol / -60 °C / Inert atmosphere 6.1: hydrogenchloride / water; tetrahydrofuran / 0.33 h / 60 °C 7.1: toluene-4-sulfonic acid / 24 h / 20 °C 8.1: toluene-4-sulfonic acid / tetrahydrofuran / 24 h / 20 °C 9.1: trichlorophosphate / -10 °C 10.1: sodium tetrahydroborate / methanol / 20 °C 11.1: 5%-palladium/activated carbon / ethanol; tetrahydrofuran / 0.75 h / Reflux View Scheme

C22H32O4 → nomegestrol acetate (58652-20-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: hydrogenchloride / water; tetrahydrofuran / 0.33 h / 60 °C 2: toluene-4-sulfonic acid / 24 h / 20 °C 3: toluene-4-sulfonic acid / tetrahydrofuran / 24 h / 20 °C 4: trichlorophosphate / -10 °C 5: sodium tetrahydroborate / methanol / 20 °C 6: 5%-palladium/activated carbon / ethanol; tetrahydrofuran / 0.75 h / Reflux View Scheme

mestranol (72-33-3) → nomegestrol acetate (58652-20-3)

Conditions

Yield

Multi-step reaction with 10 steps 1.1: triethylamine / dichloromethane / 2 h / 0 - 20 °C 2.1: sodium methylate / methanol / Reflux 2.2: 2 h / Reflux 3.1: toluene-4-sulfonic acid; trimethyl orthoformate / dichloromethane / 2 h / 20 °C 4.1: sodium; ammonia / ethanol; water; tetrahydrofuran; tert-butyl alcohol / -60 °C / Inert atmosphere 5.1: hydrogenchloride / water; tetrahydrofuran / 0.33 h / 60 °C 6.1: toluene-4-sulfonic acid / 24 h / 20 °C 7.1: toluene-4-sulfonic acid / tetrahydrofuran / 24 h / 20 °C 8.1: trichlorophosphate / -10 °C 9.1: sodium tetrahydroborate / methanol / 20 °C 10.1: 5%-palladium/activated carbon / ethanol; tetrahydrofuran / 0.75 h / Reflux View Scheme

3-methoxy-21-(phenylsulfinyl)-19-norpregna-1(2),3(4),5(10),17(20),20-pentaene → nomegestrol acetate (58652-20-3)

Conditions

Yield

Multi-step reaction with 9 steps 1.1: sodium methylate / methanol / Reflux 1.2: 2 h / Reflux 2.1: toluene-4-sulfonic acid; trimethyl orthoformate / dichloromethane / 2 h / 20 °C 3.1: sodium; ammonia / ethanol; water; tetrahydrofuran; tert-butyl alcohol / -60 °C / Inert atmosphere 4.1: hydrogenchloride / water; tetrahydrofuran / 0.33 h / 60 °C 5.1: toluene-4-sulfonic acid / 24 h / 20 °C 6.1: toluene-4-sulfonic acid / tetrahydrofuran / 24 h / 20 °C 7.1: trichlorophosphate / -10 °C 8.1: sodium tetrahydroborate / methanol / 20 °C 9.1: 5%-palladium/activated carbon / ethanol; tetrahydrofuran / 0.75 h / Reflux View Scheme

C26H38O6 → nomegestrol acetate (58652-20-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide; dihydrogen peroxide / methanol / 20 - 25 °C 2: magnesium / tetrahydrofuran / 30 - 55 °C 3: chloranil / 1,4-dioxane / 90 - 95 °C View Scheme
Multi-step reaction with 3 steps 1: sodium hydroxide; dihydrogen peroxide / methanol / 20 - 25 °C 2: magnesium / toluene / 30 - 55 °C 3: chloranil / 1,4-dioxane / 90 - 95 °C View Scheme
Multi-step reaction with 3 steps 1: sodium hydroxide; dihydrogen peroxide / methanol / 20 - 25 °C 2: magnesium / chloroform; diethyl ether / 30 - 55 °C 3: chloranil / 1,4-dioxane / 90 - 95 °C View Scheme

C26H38O7 → nomegestrol acetate (58652-20-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: magnesium / tetrahydrofuran / 30 - 55 °C 2: chloranil / 1,4-dioxane / 90 - 95 °C View Scheme
Multi-step reaction with 2 steps 1: magnesium / toluene / 30 - 55 °C 2: chloranil / 1,4-dioxane / 90 - 95 °C View Scheme

nomegestrol acetate (58652-20-3) → 6-α-methyl-3,20-dioxo-19-norpregna-4-en-17-yl acetate (32420-14-7)

Conditions	Yield
With palladium 10% on activated carbon In ethanol; cyclohexane for 3h; Reflux;	71%
With 5%-palladium/activated carbon; cyclohexene In ethanol for 2h; Reflux;	34%

nomegestrol acetate (58652-20-3) → (3R,3aS,5aS,5bR,8'R,8aR,9R,9'S,10'R,12aR,12bS,13'S,14'S,17'R)-3,17'-diacetyl-3a,13'-dimethyl-3',8-dioxo-1',2,2',3,3',3a,4,5,5a,5b,6,7,7',8,8',8a,9',10,10',11,11',12,12',12a,12b, 13',14',15',16',17'-triacontahydro-1H-spiro[benzo[fg]cyclopenta[a]anthracene-9,6'-cyclopenta[a]phenanthrene]-3,17'-diyl diacetate + (3R,3aS,5aS,5bR,8'R,8aR,9S,9'S,10'R,12aR,12bS,13'S,14'S,17'R)-3,17'-diacetyl-3a,13'-dimethyl-3',8-dioxo-1',2,2',3,3',3a,4,5,5a,5b,6,7,7',8,8',8a,9',10,10',11,11',12,12',12a,12b, 13',14',15',16',17'-triacontahydro-1H-spiro[benzo[fg]cyclopenta[a]anthracene-9,6'-cyclopenta[a]phenanthrene]-3,17'-diyl diacetate

Conditions	Yield
In toluene for 12h; Inert atmosphere; Reflux;	A 0.41 g B 2.5 g

Upstream product

• 1624-58-4 17α-hydroxy-3-methoxy-19-norpregna-1,3,5(10)-trien-20-one 
• 14328-46-2 20,20-(ethylenedioxy)-3-methoxy-17α-hydroxy-19-norpregna-1,3,5(10)-triene 
• 2137-18-0 17-alpha-Hydroxy-19-norprogesterone 
• 53-16-7 Estrone 
• 31981-44-9 17α-acetoxy-19-norpregna-4-ene-3,20-dione 
• 147508-40-5 6-formyl-3-ethoxy-17α-acetoxy-19-norpregna-3,5-diene-20-one 
• 58652-19-0 17α-acetoxy-6-methylene-19-norpregn-4-ene-3,20-dione 
• 1624-62-0 estrone 3-methyl ether 
• 72-33-3 mestranol 

Downstream Products

• 32420-14-7 6-α-methyl-3,20-dioxo-19-norpregna-4-en-17-yl acetate 

Relevant articles and documents

Preparation method of nomegestrol acetate

The invention relates to the field of organic synthesis, in particular to a preparation method of nomegestrol acetate. The preparation method for nomegestrol acetate comprises a step of subjecting a compound represented by a formula 5 to a reaction in the presence of a catalyst to prepare a compound represented by a formula 1, wherein the catalyst is selected from an Rh-Binap catalyst. According to the preparation method of the nomegestrol acetate, the Rh-Binap catalyst is innovatively used for preparing the nomegestrol acetate, the method is mild in reaction conditions and easy to operate, and the catalyst used in the reaction can be recycled and reused simply and repeatedly.

INDUSTRIAL PROCESS FOR THE SYNTHESIS OF NOMEGESTROL-ACETATE

The invention relates to the last step of a synthetic process, in which Nomegestrol- acetate of formula (I) is synthesized from 17α-acetoxy-6-methylene-19-norpregn-4-ene-3,20-dione of formula (II) in the presence of Pd/C catalyst and acetic acid in hot ethanolic solution.

Subcutaneous implants based on normegestrol derivatives

Subcutaneous implant for preventing conception for at least one year in women comprising an amount effect to prevent conception without suppressing intermontly bleeding of a steroid compound of formula I or formula II and a physiologically-tolerable pharmaceutical carrier.