192704-54-4

Basic information

• Product Name: Eplerenone intermediate A1
• Synonyms: Eplerenone intermediate A1;4'S(4'α),7'α-hexadecahydro-11'α-hydroxy-10'β,13'beta-dimethyl-3',5,20'-trioxospiro[furan-2(3H),17'β-[4,7]metheno(17H)cyclopenta[a]phenanthrene]-5'β(2'H)-carbonitrile
• CAS NO: 192704-54-4
• Molecular Formula: C24H29NO5
• Mol File: 192704-54-4.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 664.7±55.0 °C(Predicted)
• Appearance: /
• Density: 1.36±0.1 g/cm3(Predicted)
• Vapor Pressure: 0Pa at 25℃
• PKA: 5.86±0.70(Predicted)
• Water Solubility: 40mg/L at 20℃
• CAS DataBase Reference: Eplerenone intermediate A1(CAS DataBase Reference)
• NIST Chemistry Reference: Eplerenone intermediate A1(192704-54-4)
• EPA Substance Registry System: Eplerenone intermediate A1(192704-54-4)

Safety Data

• Hazardous Substances Data: 192704-54-4(Hazardous Substances Data)

Usage

Flammability and Explosibility

Nonflammable

Synthetic route

11α-hydroxyl canrenone (192569-17-8) + sodium cyanide (143-33-9) → 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)

Conditions	Yield
With sulfuric acid In ISOPROPYLAMIDE; water at 95℃; for 18.5h;	3 g

11α-hydroxyl canrenone (192569-17-8) + potassium cyanide (151-50-8) → 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)

Conditions	Yield
Stage #1: 11α-hydroxyl canrenone; potassium cyanide With sulfuric acid In ISOPROPYLAMIDE; water at 20 - 80℃; for 2 - 3h; Stage #2: With sulfuric acid In ISOPROPYLAMIDE; water at 80 - 102℃; for 2.33h;	84 g

5'R(5'α),7'β-20'-aminohexadecahydro-11'β-hydroxy-10'α,13'α-dimethyl-3',5-dioxospiro[furan-2(3H),17'α(5'H)-[7,4]metheno(4H)cyclopenta[a]phenanthrene]-5'-carbonitrile → 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)

Conditions	Yield
With hydrogenchloride In methanol; water at 0 - 80℃; for 7h;	36.5 kg

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

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) → eplerenone (107724-20-9)

Conditions	Yield
Stage #1: methanol; 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 20.25h; Heating / reflux; Stage #2: With hydrogenchloride In methanol; water Heating / reflux; Stage #3: With dipotassium hydrogenphosphate; formic acid; dihydrogen peroxide; potassium formate; acetic anhydride; methanesulfonyl chloride; triethylamine; trichloroacetonitrile more than 3 stages;	27.1%
Stage #1: methanol; 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 at 67℃; for 16 - 20h; Stage #2: With methanesulfonyl chloride; triethylamine In dichloromethane at 0℃; for 0.75h; Stage #3: With dipotassium hydrogenphosphate; formic acid; dihydrogen peroxide; potassium formate; acetic anhydride; trichloroacetonitrile more than 3 stages;	7.2 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) → 5β-cyano-11α,17-dihydroxy-3-oxo-17α-pregnane-7α,21-dicarboxylic acid, γ-lactone

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 With sodium acetate In water; acetonitrile for 3h; Heating / reflux; Stage #2: With hydrogenchloride In water pH=4.5 - 5.5;	4.5 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) + 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

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) → 7-methyl hydrogen 5β-cyano-11α,17-dihydroxy-3-oxo-17α-pregnane-7α,21-dicarboxylate, γ-lactone

Conditions	Yield
With sodium hydroxide at 20℃; for 1.5h;	3.6 g

Upstream product

• 192569-17-8 11α-hydroxyl canrenone 
• 151-50-8 potassium cyanide 
• 143-33-9 sodium cyanide 

Downstream Products

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

Relevant articles and documents

Processes for preparation of 3-keto-7alpha-alkoxycarbonyl-delta-4,5- steroids and intermediates useful therein

Multiple novel reaction schemes, novel process steps and novel intermediates are provided for the synthesis of epoxymexrenone and other compounds of Formula I wherein:-A-A- represents the group -CHR4-CHR5- or -CR4=CR5- R3, R4 and R5 are independently selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl, lower alkoxy, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, cyano, varyloxy;R1 represents an alpha-oriented lower alkoxycarbonyl or hydroxyalkyl radical;-B-B- represents the group -CHR6-CHR7- or an alpha- or beta- oriented group: where R6 and R7 are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano and aryloxy; andR8 and R9 are independently selected from the group consisting of hydrogen, hydroxy, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano and aryloxy, or R8 and R9 together comprise a carbocyclic or heterocyclic ring structure, or R8 or R9 together with R6 or R7 comprise a carbocyclic or heterocyclic ring structure fused to the pentacyclic D ring.