95716-70-4

Basic information

• Product Name: (7a,17a)-17-Hydroxy-3-oxo-pregna-4,9(11)-diene-7,21-dicarboxylicacid g-lactone methyl ester
• Synonyms: Pregna-4,9(11)-Diene-7-21-Dicarboxylic Acid,17-Hydroxy-3-Oxo,Gamma-Lactone,Methylestor,(7a,17a)-;EPLERENONE INTERMEDIATE;PREGNA-4,9(11)-DIENE-7,21-CARBOXYLICACID,17-HDROXY-3-OXO-G-LACTONE,METHYL ESTER(7A,17A);6,pregnane 4,9(11)-7 alpha diene,21-dicarboxylic acid,17-hydroxy-3-ketone,-butyrolectone,methylester cas:(intermediate of eplerenone);(7A,17A)-17-HYDROXY-3-OXO-PREGNA-4,9(11)-DIENE-7,21-DICARBOXYLICACID G-LACTONE METHYL ESTER;PREGN-4(5)9(11)-DIENE-7,21-DICARBOXYLICACID,17-HYDROXY-3-OXO-,GAMMA-LACTONE;Pregna-4,9(11)-diene-7,21-dicarboxylic acid, 17-hydroxy-3-oxo-, g-lactone, methyl ester, (7a,17a)-;6,PREGNANE 4,9(11)-7 ALPHA DIENE,21-DICARBOXYLIC ACID,17-HYDROXY-3-KETONE,-BUTYROLECTONE,METHYLESTER
• CAS NO: 95716-70-4
• Molecular Formula: C₂₄H₃₀O₅
• Molecular Weight: 398.496
• Product Categories: (intermediate of eplerenone);Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;Steroids
• Mol File: 95716-70-4.mol
• Article Data: 13

Chemical Properties

• Boiling Point: 580.2 °C at 760 mmHg
• Flash Point: 251.7 °C
• Appearance: /
• Density: 1.24 g/cm³
• Refractive Index: 1.576
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Acetone (Slightly), Chloroform (Slightly), Dichloromethane (Slightly), Methanol
• CAS DataBase Reference: (7a,17a)-17-Hydroxy-3-oxo-pregna-4,9(11)-diene-7,21-dicarboxylicacid g-lactone methyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: (7a,17a)-17-Hydroxy-3-oxo-pregna-4,9(11)-diene-7,21-dicarboxylicacid g-lactone methyl ester(95716-70-4)
• EPA Substance Registry System: (7a,17a)-17-Hydroxy-3-oxo-pregna-4,9(11)-diene-7,21-dicarboxylicacid g-lactone methyl ester(95716-70-4)

Safety Data

• Hazardous Substances Data: 95716-70-4(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 95716-70-4 differently. You can refer to the following data:
1. Intermediate in the preparation of Eplerenone and its derivatives.
2. Δ9,11-Eplerenone (Eplerenone EP Impurity C) is an intermediate in the preparation of Eplerenone and its derivatives.

InChI:InChI=1/C24H30O5/c1-22-8-4-15(25)12-14(22)13-16(21(27)28-3)20-17(22)5-9-23(2)18(20)6-10-24(23)11-7-19(26)29-24/h5,12,16,18,20H,4,6-11,13H2,1-3H3/t16-,18?,20?,22+,23+,24-/m1/s1

Synthetic route

17α-pregna-4-ene-7α,21-dicarboxylic acid-11α,17β-dihydroxy-3-oxo-γ-lactone-7-methyl ester → 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 phosphorus pentachloride; boron trifluoride diethyl etherate In tetrahydrofuran at 0℃; for 0.166667h; Reagent/catalyst; Temperature;	90.9%

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%

methyl hydrogen 17α-hydroxy-11α-(methylsulfonyl)oxy-3-oxopregn-4-ene-7α,21-dicarboxylate, γ-lactone (192704-58-8) → 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 formic acid; potassium formate; acetic anhydride at 70 - 100℃; for 19h; Inert atmosphere;	80%
With formic acid; potassium formate; acetic anhydride at 70 - 105℃; for 6.5h;	1.9 g
Stage #1: methyl hydrogen 17α-hydroxy-11α-(methylsulfonyl)oxy-3-oxopregn-4-ene-7α,21-dicarboxylate, γ-lactone With Isopropenyl acetate; toluene-4-sulfonic acid at 90℃; for 5h; Stage #2: With sodium acetate; acetic acid at 100℃; for 1h;	0.4 g

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;

methanol (67-56-1) + 7a-(1,4-dicarbonylpentenyl)-9(11)-encanrenone → 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 ozone at -50℃;	49.31%

diazomethane (186581-53-3, 908094-01-9) + 17β-hydroxypregna-4,9(11)-dien-3-one-7α,21-dicarboxylic acid γ-lactone (95716-74-8) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
In diethyl ether; dichloromethane for 0.166667h;	2.7 g

dimethyl sulfate (77-78-1) + 17β-hydroxypregna-4,9(11)-dien-3-one-7α,21-dicarboxylic acid γ-lactone (95716-74-8) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
In water; acetone at 45℃; for 3h;	50.94 g
With tetra(n-butyl)ammonium hydrogensulfate; sodium carbonate In dichloromethane; water at 20 - 25℃; for 11.5h;
Stage #1: dimethyl sulfate; 17β-hydroxypregna-4,9(11)-dien-3-one-7α,21-dicarboxylic acid γ-lactone In water; acetone at 45℃; for 3h; Stage #2: With potassium hydrogencarbonate; triethylamine In water; acetone at 45℃; for 1h;

17β-hydroxy-7α-(5'-methyl-2'-furyl)-pregna-4,9(11)-dien-3-one-21-carboxylic acid γ-lactone (610785-40-5) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium acetate; dibromantin / acetone; H2O / -10 °C 2.1: aq. HCl / CH2Cl2 / 2.5 h / 20 °C 3.1: O3/O2 / CH2Cl2; propan-2-ol / 0.17 h / -55 °C 3.2: dimethylsilfide / CH2Cl2; propan-2-ol / 0.83 h / 20 °C 4.1: 0.865 mg / H2O2; KHCO3 / H2O; methanol / 16 h / 20 °C 5.1: 50.94 g / acetone; H2O / 3 h / 45 °C View Scheme
Multi-step reaction with 3 steps 1.1: potassium acetate; dibromantin / acetone; H2O / -10 °C 2.1: O3/O2; H2O / CH2Cl2; propan-2-ol / 0.04 h / -55 °C 2.2: dimethylsilfide / CH2Cl2; propan-2-ol / 0.75 h / 20 °C 2.3: 86.1 percent / H2O2; KHCO3 / H2O; methanol / 15 h / 20 °C 3.1: 50.94 g / acetone; H2O / 3 h / 45 °C View Scheme
Multi-step reaction with 5 steps 1.1: O3/O2 / CH2Cl2; methanol / -78 °C 1.2: O2; trimethylphosphite / 1 h / 20 °C 2.1: 1.40 g / aq. HCl / 0.33 h / 20 °C 3.1: O3/O2 / CH2Cl2 / -78 - 20 °C 4.1: H2O2; KHCO3 / H2O / 1.5 h / 20 °C 5.1: 50.94 g / acetone; H2O / 3 h / 45 °C View Scheme

C25H32O6 → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 0.865 mg / H2O2; KHCO3 / H2O; methanol / 16 h / 20 °C 2: 50.94 g / acetone; H2O / 3 h / 45 °C View Scheme

17β-hydroxy-7α-(2'-hydroperoxy-2'-methoxyacetyl)-pregna-4,9(11)-dien-3-one-21-carboxylic acid γ-lactone (610785-44-9) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2O2; KHCO3 / H2O / 1.5 h / 20 °C 2: 50.94 g / acetone; H2O / 3 h / 45 °C View Scheme

17β-hydroxy-7α-(cis-4'-oxo-pent-2'-enoyl)-3-oxo-pregna-4,9(11)-diene-21-carboxylic acid γ-lactone (610785-50-7) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: aq. HCl / CH2Cl2 / 2.5 h / 20 °C 2.1: O3/O2 / CH2Cl2; propan-2-ol / 0.17 h / -55 °C 2.2: dimethylsilfide / CH2Cl2; propan-2-ol / 0.83 h / 20 °C 3.1: 0.865 mg / H2O2; KHCO3 / H2O; methanol / 16 h / 20 °C 4.1: 50.94 g / acetone; H2O / 3 h / 45 °C View Scheme
Multi-step reaction with 2 steps 1.1: O3/O2; H2O / CH2Cl2; propan-2-ol / 0.04 h / -55 °C 1.2: dimethylsilfide / CH2Cl2; propan-2-ol / 0.75 h / 20 °C 1.3: 86.1 percent / H2O2; KHCO3 / H2O; methanol / 15 h / 20 °C 2.1: 50.94 g / acetone; H2O / 3 h / 45 °C View Scheme

17β-hydroxy-7α-(trans-4'-oxo-pent-2'-enoyl)-3-oxo-pregna-4,9(11)-dien-21-carboxylic acid γ-lactone (610785-41-6) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: O3/O2 / CH2Cl2; propan-2-ol / 0.17 h / -55 °C 1.2: dimethylsilfide / CH2Cl2; propan-2-ol / 0.83 h / 20 °C 2.1: 0.865 mg / H2O2; KHCO3 / H2O; methanol / 16 h / 20 °C 3.1: 50.94 g / acetone; H2O / 3 h / 45 °C View Scheme

17β-hydroxy-7α-(cis-3'-acetoxyacryloyl)-3-oxo-pregna-4,9(11)-diene-21-carboxylic acid γ-lactone (610785-42-7) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.40 g / aq. HCl / 0.33 h / 20 °C 2: O3/O2 / CH2Cl2 / -78 - 20 °C 3: H2O2; KHCO3 / H2O / 1.5 h / 20 °C 4: 50.94 g / acetone; H2O / 3 h / 45 °C View Scheme
Multi-step reaction with 4 steps 1: 1.40 g / aq. HCl / 0.33 h / 20 °C 2: O3/O2 / CH2Cl2 / 0.02 h / -55 °C 3: H2O2; potassium bicarbonate / H2O / 18 h / 20 °C 4: 50.94 g / acetone; H2O / 3 h / 45 °C View Scheme

17β-hydroxy-7α-(trans-3'-acetoxyacryloyl)-3-oxo-pregna-4,9(11)-diene-21-carboxylic acid γ-lactone (610785-43-8) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: O3/O2 / CH2Cl2 / -78 - 20 °C 2: H2O2; KHCO3 / H2O / 1.5 h / 20 °C 3: 50.94 g / acetone; H2O / 3 h / 45 °C View Scheme
Multi-step reaction with 3 steps 1: O3/O2 / CH2Cl2 / 0.02 h / -55 °C 2: H2O2; potassium bicarbonate / H2O / 18 h / 20 °C 3: 50.94 g / acetone; H2O / 3 h / 45 °C View Scheme

C26H32O8 → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2O2; potassium bicarbonate / H2O / 18 h / 20 °C 2: 50.94 g / acetone; H2O / 3 h / 45 °C View Scheme

Δ9(11)-canrenone (95716-71-5) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: 77.7 percent / boron trifluoride diethyl etherate; EtOH; isopropanol / acetonitrile / 24 h / -18.4 °C 2.1: potassium acetate; dibromantin / acetone; H2O / -10 °C 3.1: aq. HCl / CH2Cl2 / 2.5 h / 20 °C 4.1: O3/O2 / CH2Cl2; propan-2-ol / 0.17 h / -55 °C 4.2: dimethylsilfide / CH2Cl2; propan-2-ol / 0.83 h / 20 °C 5.1: 0.865 mg / H2O2; KHCO3 / H2O; methanol / 16 h / 20 °C 6.1: 50.94 g / acetone; H2O / 3 h / 45 °C View Scheme
Multi-step reaction with 4 steps 1.1: 77.7 percent / boron trifluoride diethyl etherate; EtOH; isopropanol / acetonitrile / 24 h / -18.4 °C 2.1: potassium acetate; dibromantin / acetone; H2O / -10 °C 3.1: O3/O2; H2O / CH2Cl2; propan-2-ol / 0.04 h / -55 °C 3.2: dimethylsilfide / CH2Cl2; propan-2-ol / 0.75 h / 20 °C 3.3: 86.1 percent / H2O2; KHCO3 / H2O; methanol / 15 h / 20 °C 4.1: 50.94 g / acetone; H2O / 3 h / 45 °C View Scheme
Multi-step reaction with 6 steps 1.1: 77.7 percent / boron trifluoride diethyl etherate; EtOH; isopropanol / acetonitrile / 24 h / -18.4 °C 2.1: O3/O2 / CH2Cl2; methanol / -78 °C 2.2: O2; trimethylphosphite / 1 h / 20 °C 3.1: 1.40 g / aq. HCl / 0.33 h / 20 °C 4.1: O3/O2 / CH2Cl2 / -78 - 20 °C 5.1: H2O2; KHCO3 / H2O / 1.5 h / 20 °C 6.1: 50.94 g / acetone; H2O / 3 h / 45 °C View Scheme

C23H30O4 (188988-15-0) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 6.6 g / aq. CrO3, H2SO4 / acetone / 0.5 h / 5 °C 2: 2.7 g / CH2Cl2; diethyl ether / 0.17 h View Scheme

17β-hydroxy-7α-cyano-pregna-4,9(11)-dien-3-one-21-carboxylic acid γ-lactone (95716-72-6) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 6.9 g / DIBAH / 1,2-dimethoxy-ethane; hexane / 2 h / 5 °C 2: 6.6 g / aq. CrO3, H2SO4 / acetone / 0.5 h / 5 °C 3: 2.7 g / CH2Cl2; diethyl ether / 0.17 h View Scheme

methanol (67-56-1) + C24H27NO4 + sodium methylate (124-41-4) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Heating / reflux;

methyl hydrogen 17α-hydroxy-11α-(methylsulfonyl)oxy-3-oxopregn-4-ene-7α,21-dicarboxylate, γ-lactone (192704-58-8) → 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
With sodium acetate; acetic acid at 40 - 100℃; for 1.21667h;
With potassium acetate; trifluoroacetic acid; trifluoroacetic anhydride at 30 - 40℃; for 5h;

methyl hydrogen 17α-hydroxy-11α-(methylsulfonyl)oxy-3-oxopregn-4-ene-7α,21-dicarboxylate, γ-lactone (192704-58-8) → 3-oxo-17α-pregn-4-ene-7α,9:21,17-dicarbolactone + 7-methyl hydrogen 5β-cyano-17-hydroxy-3-oxo-17α-pregn-9(11)-ene-7α,21-dicarboxylate, γ-lactone + 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
With formic acid; potassium formate; acetic anhydride at 40 - 100℃; for 18h;

11β-hydroxymexrenone → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

9α-hydroxymexrenone → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

17β-hydroxypregna-4,9(11)-dien-3-one-7α,21-dicarboxylic acid γ-lactone (95716-74-8) → 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: 17β-hydroxypregna-4,9(11)-dien-3-one-7α,21-dicarboxylic acid γ-lactone With dimethyl sulfate In water; acetone at 45℃; for 3h; Stage #2: With potassium hydrogencarbonate; triethylamine In water; acetone at 45℃; for 1h;

11β,17β-dihydroxy-7α-nitromethyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (1398078-03-9) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: acetic acid / N,N-dimethyl-formamide / 0.5 h / 45 °C 1.2: 4 h 2.1: potassium carbonate / 0 - 20 °C 3.1: triethylamine / dichloromethane / 0 °C 4.1: potassium formate; formic acid / acetic anhydride / 100 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium nitrite / N,N-dimethyl-formamide / 1.5 h / 45 °C 1.2: 4 h 2.1: potassium carbonate / acetone / 0 - 20 °C 3.1: triethylamine / dichloromethane / 3 h / 0 - 20 °C 4.1: acetic anhydride; potassium formate; formic acid / 19 h / 70 - 100 °C / Inert atmosphere View Scheme

11β,17β-dihydroxy-7β-nitromethyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone (1398078-09-5) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium carbonate; benzalkonium chloride; nitromethane / N,N-dimethyl-formamide / 48 h / 90 °C 2.1: acetic acid / N,N-dimethyl-formamide / 0.5 h / 45 °C 2.2: 4 h 3.1: potassium carbonate / 0 - 20 °C 4.1: triethylamine / dichloromethane / 0 °C 5.1: potassium formate; formic acid / acetic anhydride / 100 °C View Scheme

9α,11α-epoxy-17β-hydroxypregn-4-en-3-one-7α,21-dicarboxylic acid γ-lactone (209253-72-5) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / 0 - 20 °C 2: triethylamine / dichloromethane / 0 °C 3: potassium formate; formic acid / acetic anhydride / 100 °C View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / acetone / 0 - 20 °C 2: triethylamine / dichloromethane / 3 h / 0 - 20 °C 3: acetic anhydride; potassium formate; formic acid / 19 h / 70 - 100 °C / Inert atmosphere View Scheme

11α-hydroxyl canrenone (192569-17-8) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium carbonate; benzalkonium chloride / N,N-dimethyl-formamide / 48 h / 90 °C 2.1: acetic acid / N,N-dimethyl-formamide / 0.5 h / 45 °C 2.2: 4 h 3.1: potassium carbonate / 0 - 20 °C 4.1: triethylamine / dichloromethane / 0 °C 5.1: potassium formate; formic acid / acetic anhydride / 100 °C View Scheme
Multi-step reaction with 5 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / 20 °C 2.1: acetic acid / N,N-dimethyl-formamide / 0.5 h / 45 °C 2.2: 4 h 3.1: potassium carbonate / 0 - 20 °C 4.1: triethylamine / dichloromethane / 0 °C 5.1: potassium formate; formic acid / acetic anhydride / 100 °C View Scheme
Multi-step reaction with 6 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / 20 °C 2.1: potassium carbonate; benzalkonium chloride; nitromethane / N,N-dimethyl-formamide / 48 h / 90 °C 3.1: acetic acid / N,N-dimethyl-formamide / 0.5 h / 45 °C 3.2: 4 h 4.1: potassium carbonate / 0 - 20 °C 5.1: triethylamine / dichloromethane / 0 °C 6.1: potassium formate; formic acid / acetic anhydride / 100 °C View Scheme
Multi-step reaction with 5 steps 1.1: potassium carbonate; benzalkonium chloride / N,N-dimethyl-formamide / 48 h / 90 - 100 °C 2.1: sodium nitrite / N,N-dimethyl-formamide / 1.5 h / 45 °C 2.2: 4 h 3.1: potassium carbonate / acetone / 0 - 20 °C 4.1: triethylamine / dichloromethane / 3 h / 0 - 20 °C 5.1: acetic anhydride; potassium formate; formic acid / 19 h / 70 - 100 °C / Inert atmosphere View Scheme

9(11)-encanrenone (41850-21-9) → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: boron trifluoride diethyl etherate / acetonitrile / 4 h / -25 - -20 °C / Inert atmosphere 2: potassium carbonate; 5,5-dibromohydantoin / tetrahydrofuran; water / 20 °C / Inert atmosphere 3: ozone / -50 °C View Scheme

7a-(1,4-dicarbonylpentenyl)-9(11)-encanrenone → 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: ozone / dichloromethane; isopropyl alcohol / -20 °C 1.2: 20 °C 2.1: potassium hydrogencarbonate / tetrahydrofuran / 10 °C View Scheme

17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4) → eplerenone (107724-20-9)

Conditions	Yield
With dipotassium hydrogenphosphate; trichloroacetamide; dihydrogen peroxide In dichloromethane at 0 - 15℃; for 24h; pH=9;	98%
With trichloroacetamide; dihydrogen peroxide; potassium acetate In dichloromethane at 10 - 15℃; for 0.75h; Temperature;	91.3%
With potassium phosphate; trichloroacetamide; dihydrogen peroxide In dichloromethane at 20℃;	85.3%

17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4) → eplerenone

Conditions	Yield
Stage #1: 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester With dipotassium hydrogenphosphate; trichloroacetamide In dichloromethane at 25℃; for 0.5 - 1.5h; Stage #2: With dihydrogen peroxide In dichloromethane at 20 - 31℃; for 6.16667 - 8.25h; Product distribution / selectivity;	86.4%
Stage #1: 17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester With trichloroacetonitrile In dichloromethane for 1h; Heating / reflux; Stage #2: With dihydrogen peroxide In dichloromethane; water for 27 - 29h; Heating / reflux;

17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4) → 9,11β-dichloro-7α-(methoxycarbonyl)-3-oxo-17α-pregn-4-ene-21,17-carbolactone

Conditions	Yield
With pyridine; sulfuryl dichloride In chlorobenzene at 0 - 20℃; for 1.5h;	41%

17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4) → 7-(methoxycarbonyl)-3-oxo-17α-pregna-4,9(11)-diene-21,17-carbolactone + 7β-(methoxycarbonyl)-3-oxo-17α-pregna-4,9(11)-diene-21,17-carbolactone

Conditions	Yield
With sodium methylate In methanol for 24h; Reflux;	A 0.78 g B 37%

17α-pregna-4,9(11)-diene-7α,21-dicarboxylic acid-17β-hydroxy-3-oxo-γ-lactone-7-methyl ester (95716-70-4) → 7-methyl hydrogen 17-hydroxy-3,12-dioxo-17α-pregna-4,9(11)-diene-7α,21-dicarboxylate, γ-lactone + 7-methyl hydrogen 12α,17-dihydroxy-3-oxo-17α-pregna-4,9(11)-diene-7α,21-dicarboxylate, γ-lactone + 7-methyl hydrogen 4α,5α:9α,11α-diepoxy,17-hydroxy-3-oxo-17α-pregnane-7α,21-dicarboxylate, γ-lactone + 7-methyl hydrogen 9α,11β,17-trihydroxy-3-oxo-17α-pregn-4-ene-7α,21-dicarboxylate, γ-lactone + eplerenone (107724-20-9)

Conditions	Yield
With dipotassium hydrogenphosphate; dihydrogen peroxide; trichloroacetonitrile In dichloromethane; water at 8 - 10℃; for 23h;	A n/a B 123 mg C n/a D 46.7 mg E 3.16 g

Upstream product

• 77-78-1 dimethyl sulfate 
• 95716-74-8 17β-hydroxypregna-4,9(11)-dien-3-one-7α,21-dicarboxylic acid γ-lactone 
• 610785-45-0 5α,17β-dihydroxy-3-oxo-pregn-9(11)-ene-7α,21-dicarboxylic acid bis-γ-lactone 
• 74-88-4 methyl iodide 
• 41850-21-9 9⁽¹¹⁾-encanrenone 
• 67-56-1 methanol 
• 192569-17-8 11α-hydroxyl canrenone 
• 209253-72-5 9α,11α-epoxy-17β-hydroxypregn-4-en-3-one-7α,21-dicarboxylic acid γ-lactone 
• 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 
• 192704-56-6 11β,17β-dihydroxy-7α-methoxycarbonyl-pregna-4-en-3-one-21-carboxylic acid, γ-lactone 
• 192704-58-8 methyl hydrogen 17α-hydroxy-11α-(methylsulfonyl)oxy-3-oxopregn-4-ene-7α,21-dicarboxylate, γ-lactone 
• 124-41-4 sodium methylate 
• 95716-72-6 17β-hydroxy-7α-cyano-pregna-4,9(11)-dien-3-one-21-carboxylic acid γ-lactone 

Downstream Products

• 107724-20-9 eplerenone 

Relevant articles and documents

Preparation method of eplerenone with high efficiency and low pollution

The invention discloses a preparation method of eplerenone with high efficiency and low pollution, and belongs to the technical field of preparation and processing of steroid hormone drugs. The methodcomprises the steps: by taking a compound I, namely delta 9,11-canrenone, as an initial raw material, carrying out 7-furyl addition, furyl ring opening and lactonization cyclization reaction to obtain 5,7-lactone, and carrying out ring opening methylation and 9,11-double bond epoxidation reaction to obtain the eplerenone. According to the method, raw materials and reagents are cheap and easy to obtain, and the method has extremely high market competitiveness in equipment investment and production cost; reagents used in the method are low in environmental pollution, and particularly cyano-containing high-toxicity compounds are not used, so that the method is greener and more environment-friendly; the production process is easy to control, high in yield, low in cost and suitable for industrial production.

Preparation method of eplerenone intermediate delta 9, 11 alkenyl ester

The invention provides a preparation method of eplerenone intermediate delta 9, 11 alkenyl ester, and the method comprises the following steps: carrying out esterification reaction on raw materials and methanesulfonyl chloride to generate methanesulfonate; and carrying out elimination reaction on the methanesulfonate to obtain an eplerenone intermediate; the method has the advantages that the process yield is about 90%, and the product purity is obviously higher than that reported in the existing literature. The delta 11, 12-alkenyl ester generated in the method has the advantages of fewer lactone impurities and high yield, and the method is an economic and environment-friendly synthetic route, greatly improves the prior art, and is suitable for industrial production.

Process for the preparation of Eplerenone

The invention belongs to the medical field, and particularly relates to a preparation method of eplerenone. The preparation method comprises the following steps: in the presence of phosphorous pentachloride and boron trihalide, performing dehydration reaction on 17alpha-pregn-4-ene-7alpha,21-dicarboxylic acid-11alpha,17beta-dihydroxy-3-oxo-gamma-lactone-7-methyl ester used as an initial raw material to obtain 17alpha-pregn-4,9(11)-diene-7alpha,21-dicarboxylic acid-17beta-hydroxyl-3-oxo-gamma-lactone and 7-methyl ester; and performing epoxidation reaction on the 17alpha-pregn-4,9(11)-diene-7alpha,21-dicarboxylic acid-17beta-hydroxyl-3-oxo-gamma-lactone and 7-methyl ester to obtain the eplerenone. The preparation method has specificity, and reduces generation of foreign matters; the obtained product is favorable in quality and high in yield, and the product purity is up to 99.5% or above; and the preparation method has the advantages of accessible raw materials, simple operation and mild reaction conditions, and is easy to implement industrial production.