192704-56-6

Basic information

• Product Name: 11-a-Hydroxy canrenone methyl ester
• Synonyms: 11-a-Hydroxy canrenone methyl ester;11-ALPHA-HYDROXY-7-ALPHA-(METHOXYCARBONYL)-3-OXOPREGN-4-ENE-21,17-ALPHA-CARBOLACTONE;(7α,11α,17α)-11,17-Dihydroxy-3-oxopregn-4-ene-7,21-dicarboxylic Acid γ-Lactone Methyl Ester;11α,17β-Dihydroxypregn-4-en-3-one 7α,21-dicarboxylic Acid γ-Lactone Methyl Ester;11α-Hydroxy Mexrenone;11α-HydroxyMexrenone;11-Alpha-Hydroxy canrenone methyl ester;Eplerenone intermediate A2
• CAS NO: 192704-56-6
• Molecular Formula: C₂₄H₃₂O₆
• Molecular Weight: 416.50728
• Product Categories: (intermediate of eplerenone)
• Mol File: 192704-56-6.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 604.5±55.0 °C(Predicted)
• Appearance: /
• Density: 1.27±0.1 g/cm3(Predicted)
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 14.40±0.70(Predicted)
• CAS DataBase Reference: 11-a-Hydroxy canrenone methyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 11-a-Hydroxy canrenone methyl ester(192704-56-6)
• EPA Substance Registry System: 11-a-Hydroxy canrenone methyl ester(192704-56-6)

Safety Data

• Hazardous Substances Data: 192704-56-6(Hazardous Substances Data)

Synthetic route

9α,11α-epoxy-17β-hydroxypregn-4-en-3-one-7α,21-dicarboxylic acid γ-lactone (209253-72-5) + methyl iodide (74-88-4) → 11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6)

Conditions	Yield
With potassium carbonate In acetone at 0 - 20℃;	80%
With potassium carbonate at 0 - 20℃;	4 g

4'S(4'α),7'α-hexadecahydro-11'α-hydroxy-10'β,13'β-dimethyl-3',5,20'-trioxospiro[furan-2(3H),17'β-[4,7]metheno(17H)cyclopenta[a]phenanthrene]-5'β(2'H)-carbonitrile (192704-54-4) + sodium methylate (124-41-4) → 11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6)

Conditions	Yield
Stage #1: 4'S(4'α),7'α-hexadecahydro-11'α-hydroxy-10'β,13'β-dimethyl-3',5,20'-trioxospiro[furan-2(3H),17'β-[4,7]metheno(17H)cyclopenta[a]phenanthrene]-5'β(2'H)-carbonitrile; sodium methylate for 20h; Heating / reflux; Stage #2: With hydrogenchloride In methanol; water	78%

methanol (67-56-1) + 4'S(4'α),7'α-hexadecahydro-11'α-hydroxy-10'β,13'β-dimethyl-3',5,20'-trioxospiro[furan-2(3H),17'β-[4,7]metheno(17H)cyclopenta[a]phenanthrene]-5'β(2'H)-carbonitrile (192704-54-4) + sodium methylate (124-41-4) → 11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6)

Conditions	Yield
Heating / reflux;	77%
With zinc(II) iodide

C24H29NO5 + potassium methanolate (865-33-8) → 11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6)

Conditions	Yield
In methanol at 62 - 115℃; Product distribution / selectivity;	68%
With Methyl formate In methanol at 60 - 115℃; for 0.05 - 11.5h; Product distribution / selectivity;	62.6%

4'S(4'α),7'α-hexadecahydro-11'α-hydroxy-10'β,13'β-dimethyl-3',5,20'-trioxospiro[furan-2(3H),17'β-[4,7]metheno(17H)cyclopenta[a]phenanthrene]-5'β(2'H)-carbonitrile (192704-54-4) + potassium methanolate (865-33-8) → 11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6)

Conditions	Yield
In methanol for 23.5h; Heating / reflux;	2.98 g
Stage #1: 4'S(4'α),7'α-hexadecahydro-11'α-hydroxy-10'β,13'β-dimethyl-3',5,20'-trioxospiro[furan-2(3H),17'β-[4,7]metheno(17H)cyclopenta[a]phenanthrene]-5'β(2'H)-carbonitrile; potassium methanolate In methanol at 60℃; for 7.5h; Heating / reflux; Stage #2: With hydrogenchloride In methanol; water for 0.25h;	25 - 27 g

Mexrenone (41020-65-9) → 11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6)

Conditions	Yield
With Beuveria bassiana ATCC 7159 In water
With Absidia coerula ATCC 6647 In water
With Aspergillus niger ATCC 16888 In water

11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6) + methanesulfonyl chloride (124-63-0) → methyl hydrogen 17α-hydroxy-11α-(methylsulfonyl)oxy-3-oxopregn-4-ene-7α,21-dicarboxylate, γ-lactone (192704-58-8)

Conditions	Yield
With triethylamine In dichloromethane at 10 - 15℃; for 2h; Reagent/catalyst; Temperature; Solvent; Inert atmosphere;	97.7%
With triethylamine In dichloromethane at -5 - 5℃; for 1.5h;	88%
With pyridine at 5 - 20℃; for 2h;	85%

11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
With hexafluoropropene-diethylamine adduct; diethyl-(pentafluoro-propenyl)-amine In chloroform at 30℃; for 30h; Solvent; Temperature; Reagent/catalyst;	90%
Stage #1: 11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone With methanesulfonyl chloride; triethylamine In dichloromethane at 5℃; for 1h; Stage #2: With formic acid; potassium formate; acetic anhydride at 70 - 95℃; for 5 - 9h;	77%
With 1H-imidazole; sulfuryl dichloride In tetrahydrofuran at -10 - 20℃; for 1.5h;	71%

11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6) → 3-oxo-17α-pregn-4-ene-7α,9:21,17-dicarbolactone + 7-methyl hydrogen 17α-hydroxy-3-oxopregna-4,11-diene-7α,21-dicarboxylate, γ-lactone (192704-70-4) + 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Stage #1: 11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone With methanesulfonyl chloride; triethylamine In dichloromethane at 0℃; for 1.41667h; Stage #2: With formic acid; potassium formate; acetic anhydride at 40 - 95℃; for 2h;	A 2.27 g B 3.72 g C 68.8%
Stage #1: 11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone With sulfuryl dichloride In tetrahydrofuran at -70℃; for 0.5h; Stage #2: With 1H-imidazole In tetrahydrofuran at -70 - 20℃; for 2h;
Stage #1: 11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone With methanesulfonyl chloride; triethylamine In dichloromethane at -5 - 0℃; for 1.33333h; Stage #2: With sodium acetate; acetic anhydride; acetic acid In dichloromethane at 55 - 135℃; for 1.5 - 2h;

11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6) → methyl hydrogen 17α-hydroxy-11α-(methylsulfonyl)oxy-3-oxopregn-4-ene-7α,21-dicarboxylate, γ-lactone (192704-58-8)

methanol (67-56-1) + 11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6) + methyl iodide (74-88-4) → dimethyl 11α17-dihydroxy-3-oxo-17α-pregn-4-ene-7α,21-dicarboxylate

Conditions	Yield
Stage #1: methanol; 11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone With potassium hydroxide at 20℃; Heating / reflux; Stage #2: methyl iodide In acetone at 20℃; for 18h;

11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6) → eplerenone (107724-20-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 0 °C 2: potassium formate; formic acid / acetic anhydride / 100 °C 3: trichloroacetamide; dihydrogen peroxide; dipotassium hydrogenphosphate / dichloromethane / 10 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: sulfuryl dichloride; 1H-imidazole / tetrahydrofuran / 1.5 h / -10 - 20 °C 2: trichloroacetamide; disodium hydrogenphosphate; dihydrogen peroxide / dichloromethane / 18 h / 15 - 20 °C View Scheme
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 3 h / 0 - 20 °C 2: acetic anhydride; potassium formate; formic acid / 19 h / 70 - 100 °C / Inert atmosphere 3: dipotassium hydrogenphosphate; dihydrogen peroxide; trichloroacetamide / dichloromethane / 24 h / 0 - 15 °C / pH 9 View Scheme

11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6) → 7-(methoxycarbonyl)-3-oxo-17α-pregna-4,9(11)-diene-21,17-carbolactone

Conditions	Yield
Multi-step reaction with 2 steps 1: sulfuryl dichloride; 1H-imidazole / tetrahydrofuran / 1.5 h / -10 - 20 °C 2: sodium methylate / methanol / 24 h / Reflux View Scheme

11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6) → 9,11α-epoxy-7β-(methoxycarbonyl)-3-oxo-17α-pregn-4-ene-21,17-carbolactone + 9,11α-epoxy-7-(methoxycarbonyl)-3-oxo-17α-pregn-4-ene-21,17-carbolactone

Conditions	Yield
Multi-step reaction with 3 steps 1: sulfuryl dichloride; 1H-imidazole / tetrahydrofuran / 1.5 h / -10 - 20 °C 2: trichloroacetamide; disodium hydrogenphosphate; dihydrogen peroxide / dichloromethane / 18 h / 15 - 20 °C 3: sodium methylate / methanol / 24 h / Reflux View Scheme

11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6) → 9,11β-dichloro-7α-(methoxycarbonyl)-3-oxo-17α-pregn-4-ene-21,17-carbolactone

Conditions	Yield
Multi-step reaction with 2 steps 1: sulfuryl dichloride; 1H-imidazole / tetrahydrofuran / 1.5 h / -10 - 20 °C 2: pyridine; sulfuryl dichloride / chlorobenzene / 1.5 h / 0 - 20 °C View Scheme

11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6) → 3-oxo-17α-pregn-4-ene-7α,9:21,17-dicarbolactone

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / 2 h / 5 - 20 °C 2: sodium acetate / acetic acid; water / 3 h / 70 °C View Scheme

11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6) → 7β-(methoxycarbonyl)-3-oxo-17α-pregna-4,9(11)-diene-21,17-carbolactone

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium methylate / methanol / 24 h / Reflux 2: sulfuryl dichloride; 1H-imidazole / tetrahydrofuran / 1.5 h / -20 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: sulfuryl dichloride; 1H-imidazole / tetrahydrofuran / 1.5 h / -10 - 20 °C 2: sodium methylate / methanol / 24 h / Reflux View Scheme

11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (192704-56-6) → 9,11α-epoxy-7β-(methoxycarbonyl)-3-oxo-17α-pregn-4-ene-21,17-carbolactone

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium methylate / methanol / 24 h / Reflux 2: sulfuryl dichloride; 1H-imidazole / tetrahydrofuran / 1.5 h / -20 - 20 °C 3: trichloroacetamide; disodium hydrogenphosphate; dihydrogen peroxide / dichloromethane / 48 h / 15 - 20 °C View Scheme
Multi-step reaction with 3 steps 1: sulfuryl dichloride; 1H-imidazole / tetrahydrofuran / 1.5 h / -10 - 20 °C 2: sodium methylate / methanol / 24 h / Reflux 3: trichloroacetamide; disodium hydrogenphosphate; dihydrogen peroxide / dichloromethane / 48 h / 15 - 20 °C View Scheme

Upstream product

• 209253-72-5 9α,11α-epoxy-17β-hydroxypregn-4-en-3-one-7α,21-dicarboxylic acid γ-lactone 
• 18107-18-1 diazomethyl-trimethyl-silane 
• 865-33-8 potassium methanolate 
• 192569-17-8 11α-hydroxyl canrenone 
• 74-88-4 methyl iodide 
• 1398078-09-5 11β,17β-dihydroxy-7β-nitromethyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone 
• 1398078-03-9 11β,17β-dihydroxy-7α-nitromethyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone 
• 685877-67-2 C₂₄H₃₄O₆ 
• 685877-52-5 C₂₈H₃₈O₈ 
• 41020-65-9 Mexrenone 
• 192704-54-4 4'S(4'α),7'α-hexadecahydro-11'α-hydroxy-10'β,13'β-dimethyl-3',5,20'-trioxospiro[furan-2(3H),17'β-[4,7]metheno(17H)cyclopenta[a]phenanthrene]-5'β(2'H)-carbonitrile 
• 67-56-1 methanol 
• 124-41-4 sodium methylate 

Downstream Products

• 95716-70-4 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester 
• 192704-70-4 7-methyl hydrogen 17α-hydroxy-3-oxopregna-4,11-diene-7α,21-dicarboxylate, γ-lactone 
• 192704-58-8 methyl hydrogen 17α-hydroxy-11α-(methylsulfonyl)oxy-3-oxopregn-4-ene-7α,21-dicarboxylate, γ-lactone 
• 107724-20-9 eplerenone 

Relevant articles and documents

A steroid compound derivative having, its preparation process and its use in the preparation of Eplerenone

The invention relates to a canrenone derivative steroid compound, a preparation method and an application in the medicine field, and particularly relates to 7alpha-nitro methyl-11alpha,17beta-dihydroxy-3-oxo-17alpha-pregna-4-ene-21-carboxylic acid-gamma-lactone (a compound shown in formula 2), a preparation method and an application in eplerenone preparation. The key steps of the invention are that nitromethane is used as a nucleophilic reagent; the alpha-nitro methyl group is introduced to the C-7 position stereoselectively so as to further construct a carboxylic acid methyl ester structure with a C-7alpha position configuration of eplerenone; the method of the invention has the characteristics of short steps, mild conditions, and low cost.

A chemobiological synthesis of eplerenone

This paper will describe an approach to the synthesis of eplerenone, which is being marketed for the treatment of hypertension. The synthesis begins with DHEA available from wild yams and uses a combination of microbiological and chemical transformations to build eplerenone. Georg Thieme Verlag Stuttgart.

Processes for preparing C-7 substituted steroids

This invention relates to processes for the preparation of novel 7-carboxy substituted steroid compounds of Formula I,