5571-36-8

Basic information

• Product Name: Estradiene dione-3-keta
• Synonyms: ESTRADIENE DIONE-3-KETA;ESTRADIENE DIONE-3-KETAL;cyclic-3-(1,2-ethanediyl acetal)-estra-5(10),9(11)-dien-3,17-dione;3-ETHYLENE DIOXY-17-OXO-13-METHYL ESTRA-5(10)9(11)-DIENE;3-ETHYLENE DIOXY-17-OXO ESTRA-5(10), 9(11)-DIENE;3-Ethylenedioxy-estra-5(10),9(11)-diene-17-one;Estradiene;-ETHYLENEDIOXY-ESTRA-5(10), 9(11)-DIEN-17-ONE
• CAS NO: 5571-36-8
• Molecular Formula: C₂₀H₂₆O₃
• Molecular Weight: 314.42
• EINECS: 427-230-8
• Product Categories: Various Intermediates;Intermediates;Intermediates & Fine Chemicals;Pharmaceuticals;Other APIs
• Mol File: 5571-36-8.mol
• Article Data: 2

Chemical Properties

• Melting Point: 152-154°C
• Boiling Point: 488.1 °C at 760 mmHg
• Flash Point: 241.2 °C
• Appearance: off-white solid
• Density: 1.2 g/cm³
• Vapor Pressure: 1.12E-09mmHg at 25°C
• Refractive Index: 1.582
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Sparingly, Heated, Sonicated), Methanol (Slightly)
• Water Solubility: 903μg/L at 25℃
• CAS DataBase Reference: Estradiene dione-3-keta(CAS DataBase Reference)
• NIST Chemistry Reference: Estradiene dione-3-keta(5571-36-8)
• EPA Substance Registry System: Estradiene dione-3-keta(5571-36-8)

Safety Data

• RIDADR: 3077
• HazardClass: 9
• PackingGroup: III
• Hazardous Substances Data: 5571-36-8(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

Mifepristone intermediate; antiprogestational antiglucocorticoid antagonist steroidal spirooxazole.

InChI:InChI=1/C20H26O3/c1-19-8-6-15-14-7-9-20(22-10-11-23-20)12-13(14)2-3-16(15)17(19)4-5-18(19)21/h6,16-17H,2-5,7-12H2,1H3/t16-,17+,19+/m1/s1

Synthetic route

(8S,13S,14S,17S)-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2'-[1,3]dioxolan]-17-ol (53303-91-6) → ethylene deltenone (5571-36-8)

Conditions	Yield
With tetrapropylammonium perruthennate; 4-methylmorpholine N-oxide In dichloromethane for 0.25h; Ambient temperature;	99.3%

ethylene glycol (107-21-1) + 17-hydroxy-estra-4,9-dien-3-one → ethylene deltenone (5571-36-8)

Conditions	Yield
With toluene-4-sulfonic acid; orthoformic acid triethyl ester; pyridinium chlorochromate 2.) CH2Cl2; Yield given. Multistep reaction;

4,9-Androstadiene-3,17-dione (5173-46-6) → ethylene deltenone (5571-36-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaBH4 / tetrahydrofuran; methanol / -10 °C 2: 1.) (EtO)3CH, pTsOH, 2.) pyridinium chlorochromate / 2.) CH2Cl2 View Scheme

17β-hydroxyestra-4,9-dien-3-one (6218-29-7) → ethylene deltenone (5571-36-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 92 percent / H2SO4 / benzene; CH2Cl2 / 2.5 h / Heating 2: 99.3 percent / N-methylmorpholine N-oxide, (nC3H7)4NRuO4 / CH2Cl2 / 0.25 h / Ambient temperature View Scheme

ethylene deltenone (5571-36-8) → (8S,13S,14S,17S)-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2'-[1,3]dioxolan]-17-ol (53303-91-6)

Conditions	Yield
With sodium tetrahydroborate In tetrahydrofuran; methanol at 0 - 25℃; for 1.5h; Inert atmosphere;	100%
With sodium tetrahydroborate In methanol for 0.25h; Ambient temperature;	98%
With sodium hydroxide; sodium tetrahydroborate In methanol; water at 2℃; for 2.08333h;
With potassium borohydride; butan-1-ol at 30℃; Reagent/catalyst; Temperature;	9.3 g
With sodium tetrahydroborate In tetrahydrofuran; methanol at 0 - 20℃; for 1.5h;

N,N-phenylbistrifluoromethane-sulfonimide (37595-74-7) + ethylene deltenone (5571-36-8) → 17-[[(trifluoromethyl)sulfonyl]oxy]estra-5(10),9(11),16-trien-3-one cyclic 1,2-ethanediyl acetal (866004-28-6)

Conditions	Yield
Stage #1: ethylene deltenone With lithium hexamethyldisilazane In tetrahydrofuran at -15℃; for 0.5h; Stage #2: N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran at 0℃; for 3h; Further stages.;	100%
Stage #1: ethylene deltenone With lithium hexamethyldisilazane In tetrahydrofuran at -40 - -15℃; for 0.5h; Stage #2: N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran at -15 - 0℃; for 3h; Stage #3: With sodium hydrogencarbonate In tetrahydrofuran; water	100%

sodium acetylide + ethylene deltenone (5571-36-8) → (8S,13S,14S,17R)-17-ethynyl-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2’-[1,3]dioxolan]-17-ol (5490-76-6)

Conditions	Yield
In tetrahydrofuran at 0℃;	100%

ethylene deltenone (5571-36-8) → (8S,13S,14S)-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2’-[1,3] dioxolan]-17-ol

Conditions	Yield
With methanol; sodium tetrahydroborate at 20℃;	100%
With methanol; sodium tetrahydroborate In tetrahydrofuran at 0 - 20℃; for 1.5h;	100%
With methanol; sodium tetrahydroborate In tetrahydrofuran at 0 - 20℃; for 1.5h;

sodium acetylide (1066-26-8) + ethylene deltenone (5571-36-8) → (8S,13S,14S,17R)-17-ethynyl-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2’-[1,3]dioxolan]-17-ol (5490-76-6)

Conditions	Yield
In tetrahydrofuran at -2 - 0℃; for 6.5h; Inert atmosphere; Industrial scale;	99%
In tetrahydrofuran at -2 - 0℃; for 6h; Inert atmosphere; Large scale;	99%
In tetrahydrofuran at 0℃; for 1h; Inert atmosphere;	95%

Pentafluoroethyl iodide (354-64-3) + ethylene deltenone (5571-36-8) → 3,3-ethylenedioxy-17β-hydroxy-17-(1,1,2,2,2-pentafluoroethyl)-estra-5(10),9(11)-diene (1421036-65-8)

Conditions	Yield
Stage #1: Pentafluoroethyl iodide; ethylene deltenone In toluene at -78℃; for 0.166667h; Stage #2: With methyllithium lithium bromide In diethyl ether; toluene at -78 - 0℃; for 2.08333h;	85%

diethyl cyanophosphonate (2942-58-7) + ethylene deltenone (5571-36-8) → 17-cyano-3,3-[1,2-ethanediylbis(oxy)]estra-5(10),9(11)-diene (240806-36-4)

Conditions	Yield
Stage #1: diethyl cyanophosphonate; ethylene deltenone With lithium cyanide In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: With samarium diiodide In tetrahydrofuran; tert-butyl alcohol for 3.5h; Further stages.;	79%
Stage #1: diethyl cyanophosphonate; ethylene deltenone With lithium cyanide In tetrahydrofuran at 20℃; for 0.5h; Stage #2: With samarium diiodide; tert-butyl alcohol In tetrahydrofuran Inert atmosphere;	79%

ethylene deltenone (5571-36-8) → (5'R,10'R,13'S)-13'-methyl-1',2',6',7',8',12',13',14',15',16'-decahydro-17'H-spiro[1,3-dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-one (39931-88-9, 116003-08-8, 39931-87-8)

Conditions	Yield
With 1,1,1,3,3,3-hexachloro-propan-2-one; dihydrogen peroxide In dichloromethane for 72h;	76.1%
With disodium hydrogenphosphate; dihydrogen peroxide; Hexafluoroacetone In dichloromethane at 0 - 4℃; for 18h;	59.76%
With disodium hydrogenphosphate; dihydrogen peroxide; Hexafluoroacetone In dichloromethane at 0 - 20℃; for 18h;	53%

ethylene deltenone (5571-36-8) → 3-(ethylenedioxy)estra-5,10-epoxy-9(11)-ene-17-one (786698-67-7)

Conditions	Yield
With pyridine; dihydrogen peroxide; Hexafluoroacetone In dichloromethane at 20℃; for 16h;	74%

2,2-dimethyl-3-butyne (917-92-0) + ethylene deltenone (5571-36-8) → (8S,13S,14S,17S)-17-(3,3-dimethylbut-1-yn-1-yl)-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2’-[1,3]dioxolan]-17-ol

Conditions	Yield
Stage #1: 3,3-Dimethylbut-1-yne With n-butyllithium In tetrahydrofuran at -78℃; for 0.416667h; Stage #2: ethylene deltenone In tetrahydrofuran at -78 - 20℃; for 0.95h;	74%
Stage #1: 3,3-Dimethylbut-1-yne With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.416667h; Inert atmosphere; Stage #2: ethylene deltenone In tetrahydrofuran; hexane at -78 - 25℃; for 0.95h; Inert atmosphere;	74%

1,1-dibromo-3-methyl-1-butene (32363-92-1) + ethylene deltenone (5571-36-8) → estra-5(10),9(11)-dien-3-one, 17β-hydroxy-17α-(3-methyl-1-butynyl) cyclic 3-(1,2-ethanediyl acetal) (264129-99-9)

Conditions	Yield
Stage #1: 1,1-dibromo-3-methyl-1-butene With n-butyllithium In tetrahydrofuran; hexane at -40℃; for 2h; Metallation; Stage #2: ethylene deltenone In tetrahydrofuran; hexane at 25℃; for 8h; Alkynylation;	71%

[(p-methylphenyl)sulfonylmethyl]isonitrile (38622-91-2, 36635-61-7) + ethylene deltenone (5571-36-8) → 17-cyano-3,3-[1,2-ethanediylbis(oxy)]estra-5(10),9(11)-diene (240806-36-4)

Conditions	Yield
With potassium tert-butylate In 1,2-dimethoxyethane; tert-butyl alcohol for 2.5h;	71%

ethylene deltenone (5571-36-8) → (5'R,10'R,13'S)-13'-methyl-1',2',6',7',8',12',13',14',15',16'-decahydro-17'H-spiro[1,3-dioxolane-2,3'-[5,10]epoxycyclopenta[a]phenanthren]-17'-one (39931-88-9, 116003-08-8, 39931-87-8) + 3,3-(ethylenedioxy)-5β,10β-epoxyestra-9(11)-ene-17-one (39931-88-9)

Conditions	Yield
With pyridine; dihydrogen peroxide In dichloromethane at 0℃; for 18h; Inert atmosphere;	A 68% B 13%
With pyridine; dihydrogen peroxide; Hexafluoroacetone In dichloromethane at 0 - 20℃; for 18h; optical yield given as %de;	A 56% B 18%
With pyridine; dihydrogen peroxide; Hexafluoroacetone In dichloromethane at 0℃; for 18h; Inert atmosphere;	A 56% B 18%

N-[(trifluoromethyl)sulfanyl]aniline (1045821-71-3) + ethylene deltenone (5571-36-8) → cyclic-3-(1,2-ethanediylacetal)-estra-5(10),9(11)-dien-16,16-bis((trifluoromethyl)thio)-3,17-dione

Conditions	Yield
With acetyl chloride In 1-methyl-pyrrolidin-2-one at 20℃; for 15h; Inert atmosphere;	65%

Methyltriphenylphosphonium bromide (1779-49-3) + ethylene deltenone (5571-36-8) → (8S,13S,14S)-13-methyl-17-methylene-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2'-[1,3]dioxolane]

Conditions	Yield
Stage #1: Methyltriphenylphosphonium bromide With potassium tert-butylate In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: ethylene deltenone In tetrahydrofuran at 20℃; for 18h; Inert atmosphere;	65%

ethylene deltenone (5571-36-8) → (8S,13S,14S)-16-bromo-13-methyl-1,4,6,7,8,12,13,14,15,16-decahydrospiro[cyclopenta [a]phenanthrene-3,2'-[1,3]dioxolan]-17(2H)-one

Conditions	Yield
Stage #1: ethylene deltenone With chloro-trimethyl-silane; lithium diisopropyl amide In tetrahydrofuran at -78 - 20℃; for 1.5h; Inert atmosphere; Sealed tube; Stage #2: With N-Bromosuccinimide In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Sealed tube;	64%

1,1,1,3,3,3-hexafluoro-2-propanone trihydrate + aqueous Na2 S2 O3 + Na2 HPO4 + dihydrogen peroxide (7722-84-1) + ethylene deltenone (5571-36-8) → 3,3-[1,2-Ethanediylbis(oxy)]-5α,10α-(oxido)estr-9(11)-en-17-one + 11β-[4-(N,N-Dimethylamino)phenyl]-17β-nitroestra-4,9-dien-3-one (244304-80-1)

Conditions	Yield
In diethyl ether; dichloromethane; ethyl acetate	A 53% B n/a

methylenedimethyl sulfurane (6814-64-8, 40651-06-7) + ethylene deltenone (5571-36-8) → spiro-2'-(1'-oxacyclopropane)-17(S)-<3,3-(ethylenedioxy)-5(10),9(11)-estradiene> (67308-78-5)

Conditions	Yield
In tetrahydrofuran; dimethyl sulfoxide	38.8%

ethylene deltenone (5571-36-8) + acetylene (74-86-2) → (8S,13S,14S,17R)-17-ethynyl-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2’-[1,3]dioxolan]-17-ol (5490-76-6)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran
Stage #1: acetylene With potassium tert-butylate In tetrahydrofuran at -5 - 5℃; for 1h; Stage #2: ethylene deltenone In tetrahydrofuran for 1h;

Upstream product

• 6218-29-7 17β-hydroxyestra-4,9-dien-3-one 
• 107-21-1 ethylene glycol 
• 5173-46-6 4,9-Androstadiene-3,17-dione 
• 53303-91-6 (8S,13S,14S,17S)-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2'-[1,3]dioxolan]-17-ol 

Downstream Products

• 196881-39-7 C₄₀H₄₅NO₇ 
• 196881-38-6 C₃₆H₄₀O₈S 
• 196881-37-5 C₃₇H₄₅NO₆S 
• 162607-85-4 C₃₈H₄₈N₂O₄ 
• 91934-88-2 C₃₆H₄₃NO₄ 
• 216372-21-3 3,3-ethylenedioxy-11β-[4-(2-methyl-1,3-dioxolan-2-yl)phenyl]spiro[estr-9-en-17β,2'-oxirane] 
• 216372-24-6 3,3-ethylenedioxy-5α,17β-dihydroxy-11β-[4-(N,N-dimethylamino)phenyl]-19-nor-17α-pregn-9-ene-21-carbonitrile 
• 151424-85-0 3,3-ethylenedioxy-5α-hydroxy-11β-{4'-[1',1'-(ethylenedioxy)-ethyl]phenyl}-estr-9-ene-17-one 
• 93678-27-4 3,3-ethylenedioxy-11β-[4-(N,N-dimethylamino)phenyl]spiro[estr-9-en-17β,2'-oxirane] 
• 264130-02-1 11β-(2-methyl-2-phenyl-1,3-dioxalan)-17α-(3-methyl-1-butynyl)-estra-9-en-5α,17β-diol-3-one, cyclic 1,2-ethandiyl acetal 
• 264130-01-0 11β-[4-(N,N-dimethylamino)-phenyl]-17α-(3-methyl-1-butynyl)-estra-9-en-5α,17β-diol-3-one, cyclic 1,2-ethandiyl acetal 
• 340023-82-7 3,3-[1,2-ethanediylbis(oxy)]-11β-{4-{1,1-[1,2-ethanediylbis(oxy)]ethyl}phenyl}-5α-hydroxy-17α-(3-hydroxypropyl)-19-norpregn-9-en-20-one 

Relevant articles and documents

11,21-Bisphenyl-19-norpregnane derivatives are selective antiglucocorticoids

An efficient eight-step synthesis of 11,21-bisphenyl-19-norpregnane derivatives (10) starting from 19-norandrosta-4,9-diene-3,17-dione (5) is described. It is shown that specific combinations of polar substitutions on the 11- and the 21-phenylring in compounds (10) lead to selective antiglucocorticoids with relative high binding to the glucocorticoid receptor and almost negligible binding to the progesterone receptor.