848-04-4

Basic information

• Product Name: Ethylmetrienone
• Synonyms: ETHYLMETRIENONE;13-Ethyl-3-methoxygona-1,3,5(10)-trien-17-one;18-Methylestrone methyl ether;(8R,9S,13S,14S)-13-ethyl-3- methoxy-6,7,8,9,11,12,13,14,15,16 -decahydro-17H-cyclopenta[a]phenanthren-17-one
• CAS NO: 848-04-4
• Molecular Formula: C₂₀H₂₆O₂
• Molecular Weight: 298.42
• Mol File: 848-04-4.mol
• Article Data: 12

Chemical Properties

• Boiling Point: 439.883 °C at 760 mmHg
• Flash Point: 185.526 °C
• Appearance: /
• Density: 1.083
• Solubility: Acetone, DCM, Ethyl Acetate
• CAS DataBase Reference: Ethylmetrienone(CAS DataBase Reference)
• NIST Chemistry Reference: Ethylmetrienone(848-04-4)
• EPA Substance Registry System: Ethylmetrienone(848-04-4)

Safety Data

• Hazardous Substances Data: 848-04-4(Hazardous Substances Data)

Usage

Description

Ethylmetrienone, also known as 18-Methylestrone Methyl Ether, is a synthetic steroidal compound that serves as an intermediate in the synthesis of various pharmaceuticals. It possesses a unique chemical structure that allows it to be used in the development of gestational agents with progesterone-like activity.

Uses

Used in Pharmaceutical Industry:
Ethylmetrienone is used as an intermediate in the synthesis of gestodene (G368250), an orally active gestogen with a progesterone-like profile of activity. This makes it a valuable component in the development of medications for various reproductive health applications, including hormone replacement therapy and treatment of certain gynecological conditions.

Synthetic route

(+)-17β-hydroxy-13β-ethyl-3-methoxygona-1,3,5(10)-triene (3625-82-9) → dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4)

Conditions	Yield
With tetrapropylammonium perruthennate; 4 A molecular sieve; 4-methylmorpholine N-oxide In dichloromethane for 0.5h; Ambient temperature;	97%
With tetrapropylammonium perruthennate; 4 A molecular sieve; 4-methylmorpholine N-oxide In dichloromethane for 0.5h;	95%
With chromium(VI) oxide; sulfuric acid In acetone

jones reagent + (+)-17β-hydroxy-13β-ethyl-3-methoxygona-1,3,5(10)-triene (3625-82-9) → dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4)

Conditions	Yield
In water; isopropyl alcohol; acetone

levonorgestrel (797-63-7) → dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 98 percent / Ag2CO3, Celite / toluene / Heating 2: (NH4)2Ce(NO3)6, I2 / 2.5 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 98 percent / Ag2CO3, Celite / toluene / Heating 2: 1) (NH4)2Ce(NO3)6, I2, 2) H2 / 2) 5percent Pd/CaCO3 / 1) reflux, 2.5 h, 2) ethyl acetate, 40 psi, overnight View Scheme
Multi-step reaction with 4 steps 1: 98 percent / Ag2CO3, Celite / toluene / Heating 3: 85 percent / 1 N aq. KOH / tetrahydrofuran; methanol / 1 h / Ambient temperature 4: 97 percent / N-methylmorpholine N-oxide, tetrapropylammonium perruthenate, molecular sieves 4 Angstroem / CH2Cl2 / 0.5 h / Ambient temperature View Scheme

13β-ethyl-3-hydroxygona-1,3,5(10)-trien-17-one (6544-68-9) + dimethyl sulfate (77-78-1) → dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4)

Conditions	Yield
In acetone Reflux;	29 g

2-ethyl-1,3-cyclopentanedione (823-36-9) → dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4)

Conditions	Yield
Multi-step reaction with 8 steps 1: triethylenediamine / xylene 2: aq. HCl / methanol 3: NaBH4 / methanol 4: H2 / Raney-Ni / dioxane 5: Py 6: KOH / methanol 7: Li, liq. NH3 / diethyl ether; dioxane 8: CrO3, aq. H2SO4 / acetone View Scheme

(+/-)-13-ethyl-3-methoxygona-1,3,5(10),8,14-pentaen-17-one (848-07-7) → dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4)

Conditions	Yield
Multi-step reaction with 6 steps 1: NaBH4 / methanol 2: H2 / Raney-Ni / dioxane 3: Py 4: KOH / methanol 5: Li, liq. NH3 / diethyl ether; dioxane 6: CrO3, aq. H2SO4 / acetone View Scheme

2-[2-(3,4-dihydro-6-methoxy-1(2H)-naphthalenylidene)ethyl]-2-ethyl-1,3-cyclopentanedione (850-92-0) → dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4)

Conditions	Yield
Multi-step reaction with 7 steps 1: aq. HCl / methanol 2: NaBH4 / methanol 3: H2 / Raney-Ni / dioxane 4: Py 5: KOH / methanol 6: Li, liq. NH3 / diethyl ether; dioxane 7: CrO3, aq. H2SO4 / acetone View Scheme

dl-3-Methoxy-13β-ethyl-gona-1,3,5(10),8,14-pentaen-17β-ol (2911-80-0, 14507-45-0, 15419-27-9, 24508-13-2) → dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: H2 / Raney-Ni / dioxane 2: Py 3: KOH / methanol 4: Li, liq. NH3 / diethyl ether; dioxane 5: CrO3, aq. H2SO4 / acetone View Scheme

13β-ethyl-gon-4-en-3,17-dione (21800-83-9) → dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4)

Conditions	Yield
Multi-step reaction with 3 steps 2: 85 percent / 1 N aq. KOH / tetrahydrofuran; methanol / 1 h / Ambient temperature 3: 97 percent / N-methylmorpholine N-oxide, tetrapropylammonium perruthenate, molecular sieves 4 Angstroem / CH2Cl2 / 0.5 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: lithium bromide; copper(I) bromide / acetonitrile / 17 h / 5 - 25 °C / Inert atmosphere 2: acetone / Reflux View Scheme

18-methyl-3-methoxy-1,3,5(10),8-estratetraen-17β-ol (7443-72-3) → dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: Li, liq. NH3, PhNH2 / tetrahydrofuran 2: CrO3, aq. H2SO4 / acetone View Scheme
Multi-step reaction with 2 steps 1: Li, liq. NH3 / diethyl ether; dioxane 2: CrO3, aq. H2SO4 / acetone View Scheme

methanol (67-56-1) + 13β-ethyl-gon-4-en-3,17-dione (21800-83-9) → dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) + D-(+)-13β-ethyl-3-methoxygona-1,3,5(10)-triene-6,17-dione

Conditions	Yield
With copper(ll) bromide for 1h; Heating;	A 12% B 17.56%
With ammonium cerium(IV) nitrate; hydrogen; iodine; Lindlar's catalyst 1) reflux, 2.5 h, 2) ethyl acetate, 40 psi, overnight; Yield given. Multistep reaction. Yields of byproduct given;

D-(+)-13β-ethyl-3-methoxygona-1,3,5(10)-trien-17β-yl trifluoroacetate (162210-67-5) → dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / 1 N aq. KOH / tetrahydrofuran; methanol / 1 h / Ambient temperature 2: 97 percent / N-methylmorpholine N-oxide, tetrapropylammonium perruthenate, molecular sieves 4 Angstroem / CH2Cl2 / 0.5 h / Ambient temperature View Scheme

l-3-Methoxy-13β-ethyl-gona-1,3,5(10),8-tetraen-17β-ol-hydrogensuccinat (10051-99-7) → dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: KOH / methanol 2: Li, liq. NH3 / diethyl ether; dioxane 3: CrO3, aq. H2SO4 / acetone View Scheme

(+/-)-13-ethyl-3-methoxygona-1,3,5(10),8-tetraen-17β-ol → dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: Py 2: KOH / methanol 3: Li, liq. NH3 / diethyl ether; dioxane 4: CrO3, aq. H2SO4 / acetone View Scheme

methanol (67-56-1) + 13β-ethyl-gon-4-en-3,17-dione (21800-83-9) → dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) + 13-Ethyl-3-methoxygona-1,3,5(10),9(11)-tetraen-17-one (19882-75-8) + D-(+)-13β-ethyl-3-methoxygona-1,3,5(10)-triene-6,17-dione

Conditions	Yield
With ammonium cerium(IV) nitrate; iodine for 2.5h; Heating; Yields of byproduct given;	A n/a B n/a C 0.38 g

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) + toluene-4-sulfonic acid hydrazide (1576-35-8) → 3-Methoxy-18-methyl-17-tosylhydrazono-1,3,5(10)-oestratrien (59126-70-4)

Conditions	Yield
With sulfuric acid In methanol for 14h; Heating;	88%

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) + acetylene (74-86-2) → 13β-ethyl-3-methoxy-17α-ethynyl-gona-1,3,5(10)-trien-17β-ol (14009-70-2)

Conditions	Yield
Stage #1: acetylene With potassium tert-butylate In tetrahydrofuran at 0 - 5℃; for 2h; Stage #2: dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one In tetrahydrofuran at 0 - 5℃;	78.3%
With lithium; ethylenediamine In tetrahydrofuran

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → (17S)-13β-Ethyl-3-methoxy-1,3,5(10)-gonatrien-17-spirooxiran (87080-88-4)

Conditions	Yield
	73%

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → 13-ethyl-3-methoxygonan-1,3,15-trien-17-ol

Conditions	Yield
With 1-[4-(N,N-dimethylamino)phenyl]ethanol; zirconium(IV) tert-butoxide In toluene at 23℃; for 120h;	19%

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) + Methyltriphenylphosphonium bromide (1779-49-3) → (8R,9S,13S,14S)-13-Ethyl-3-methoxy-17-methylene-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene

Conditions	Yield
(i) PhLi, (ii) /BRN= 2059135/; Multistep reaction;

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) + 1,4-Dichloro-2-butyne (821-10-3) + methyl iodide (74-88-4) → (8R,9S,13S,14S,17S)-13-Ethyl-3-methoxy-17-penta-1,3-diynyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-ol

Conditions	Yield
(i) NaNH2, liq. NH3, (ii) /BRN= 969135/, (iii) /BRN= 2059135/, THF; Multistep reaction;

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → 3-Methoxy-18-methyl-1,3,5(10),16-oestratetraen (59126-71-5)

Conditions	Yield
With methyllithium In diethyl ether for 4h; Ambient temperature; Yield given;

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) + phenyllithium (591-51-5) → 13α-Ethyl-3-methoxy-17-phenyl-1,3,5(10),14(15),16(17)-gonapentaene (126971-24-2)

Conditions	Yield
With trifluoroacetic acid 1.) THF, benzene, -78 deg C, 15 min; r.t., 30 min, 2.) CH2CL2, r.t., 1 h; Yield given. Multistep reaction;

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → 13β-ethyl-3-hydroxygona-1,3,5(10)-trien-17-one (6544-68-9)

Conditions	Yield
With pyridine; hydrogenchloride at 180℃;

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → 16α,17α-Epoxy-3-methoxy-18-methyl-1,3,5(10)-oestratrien (59126-72-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature View Scheme

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → 3-Methoxy-18-methyl-1,3,5(10),15-oestratetraen-17α-ol (59126-63-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 87 percent / ethane-1,2-diol / 24 h / 120 °C 4: m-chlorperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 2 h / Ambient temperature 5: 30 percent / o-xylene / 33 h / 140 °C View Scheme
Multi-step reaction with 3 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 65 percent / diphenyl diselenide, NaBH4 / ethanol / 18 h / Heating View Scheme
Multi-step reaction with 5 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 59 percent / lithium bromide / acetic acid / 2 h / Ambient temperature 4: 88 percent / phosphor trichloride oxide / tetrahydrofuran / 18 h / Ambient temperature 5: 1) 1,8-diazobicyclo<5.4.0>undec-7-en; 2) oxalic acid / 1) 30 h at 140 deg C; 2) methanol, water, 24 h at room temp. View Scheme
Multi-step reaction with 5 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 79 percent / NaBH4 / ethanol / 80 °C / 1) 20 min.; 2) 17 h 4: 12 percent / NaIO4 / methanol; CH2Cl2 / 48 h / Ambient temperature 5: 50 percent / NaCO3 / o-xylene / 20 h / 140 °C View Scheme

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → 16β-Brom-3-methoxy-18-methyl-1,3,5(10)-oestratrien-17α-ol (59126-79-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 59 percent / lithium bromide / acetic acid / 2 h / Ambient temperature View Scheme

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → 3-Methoxy-18-methyl-1,3,5(10),14,16-oestrapentaen (80904-55-8)

Conditions	Yield
Multi-step reaction with 6 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 87 percent / ethane-1,2-diol / 24 h / 120 °C 4: m-chlorperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 2 h / Ambient temperature 5: 30 percent / o-xylene / 33 h / 140 °C 6: 55 percent / 70 percent HClO4 / acetone / 0.33 h / Ambient temperature View Scheme
Multi-step reaction with 4 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 65 percent / diphenyl diselenide, NaBH4 / ethanol / 18 h / Heating 4: 55 percent / 70 percent HClO4 / acetone / 0.33 h / Ambient temperature View Scheme
Multi-step reaction with 6 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 59 percent / lithium bromide / acetic acid / 2 h / Ambient temperature 4: 88 percent / phosphor trichloride oxide / tetrahydrofuran / 18 h / Ambient temperature 5: 1) 1,8-diazobicyclo<5.4.0>undec-7-en; 2) oxalic acid / 1) 30 h at 140 deg C; 2) methanol, water, 24 h at room temp. 6: 55 percent / 70 percent HClO4 / acetone / 0.33 h / Ambient temperature View Scheme
Multi-step reaction with 6 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 79 percent / NaBH4 / ethanol / 80 °C / 1) 20 min.; 2) 17 h 4: 12 percent / NaIO4 / methanol; CH2Cl2 / 48 h / Ambient temperature 5: 50 percent / NaCO3 / o-xylene / 20 h / 140 °C 6: 55 percent / 70 percent HClO4 / acetone / 0.33 h / Ambient temperature View Scheme

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → 3-Methoxy-18-methyl-16β-phenylthio-1,3,5(10)-oestratrien-17α-ol (80904-56-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 79 percent / NaBH4 / ethanol / 80 °C / 1) 20 min.; 2) 17 h View Scheme

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → 3-Methoxy-18-methyl-16β-phenylselenyl-1,3,5(10)-oestratrien-17α-ol (80904-57-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 95 percent / NaBH4 / ethanol / 1) room temp.; 2) reflux at 20 h View Scheme

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → 3-Methoxy-18-methyl-16β-piperidino-1,3,5(10)-oestratien-17α-ol (80904-53-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 87 percent / ethane-1,2-diol / 24 h / 120 °C View Scheme

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → N-(17α-Hydroxy-3-methoxy-1,3,5(10)-oestratrien-16β-yl)piperidin-N-oxid (80904-54-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 87 percent / ethane-1,2-diol / 24 h / 120 °C 4: m-chlorperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 2 h / Ambient temperature View Scheme

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → 16β-Brom-3-methoxy-18-methyl-17α-(tetrahydro-2-pyranyloxy)-1,3,5(10)-oestratrien (59126-80-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 59 percent / lithium bromide / acetic acid / 2 h / Ambient temperature 4: 88 percent / phosphor trichloride oxide / tetrahydrofuran / 18 h / Ambient temperature View Scheme

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → 3-Methoxy-18-methyl-16β-phenylsulfonyl-1,3,5(10)-oestratrien-17α-ol (80904-62-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 79 percent / NaBH4 / ethanol / 80 °C / 1) 20 min.; 2) 17 h 4: 4 percent / NaIO4 / methanol; CH2Cl2 / 48 h / Ambient temperature View Scheme

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → 3-Methoxy-18-methyl-16β-phenylselenonyl-1,3,5(10)-oestratrien-17α-ol (80904-63-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 95 percent / NaBH4 / ethanol / 1) room temp.; 2) reflux at 20 h 4: 6 percent / m-chlorperbenzoic acid / CH2Cl2 / 0.25 h / -40 °C View Scheme

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → (S)-3-Methoxy-18-methyl-16β-phenylsulfinyl-1,3,5(10)-oestratrien-17α-ol (80904-58-1, 80904-60-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 79 percent / NaBH4 / ethanol / 80 °C / 1) 20 min.; 2) 17 h 4: 34 percent / NaIO4 / methanol; CH2Cl2 / 48 h / Ambient temperature View Scheme

dl-13-ethyl-3-methoxygona-1,3,5(10)-trien-17-one (848-04-4) → (R)-3-Methoxy-18-methyl-16β-phenylsulfinyl-1,3,5(10)-oestratrien-17α-ol (80904-58-1, 80904-60-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: methyl lithium / diethyl ether / 4 h / Ambient temperature 2: 79 percent / 4-nitroperbenzoic acid / 1,2-dichloro-ethane; 2-methyl-propan-2-ol / 18 h / Ambient temperature 3: 79 percent / NaBH4 / ethanol / 80 °C / 1) 20 min.; 2) 17 h 4: 12 percent / NaIO4 / methanol; CH2Cl2 / 48 h / Ambient temperature View Scheme

Upstream product

• 848-07-7 (+/-)-13-ethyl-3-methoxygona-1,3,5⁽¹⁰⁾,8,14-pentaen-17-one 
• 968-74-1 (+/-)-3-Methoxy-13β-ethylgona-1,3,5(10)-trien-17-on 
• 848-04-4 dl-13-ethyl-3-ethoxygona-1,3,5⁽¹⁰⁾-trien-17-one 
• 80482-67-3 (-)-(R)-N,S-dimethyl-S-phenylsulfoximine 
• 2911-80-0 dl-3-Methoxy-13β-ethyl-gona-1,3,5(10),8,14-pentaen-17β-ol 
• 27984-96-9 C₂₀H₂₆O₃ 
• 850-92-0 2-[2-(3,4-dihydro-6-methoxy-1(2H)-naphthalenylidene)ethyl]-2-ethyl-1,3-cyclopentanedione 
• 823-36-9 2-ethylcyclopentane-1,3-dione 
• 848-01-1 dl-3-Methoxy-13β-ethyl-gona-1,3,5(10)-trien-17β-ol 
• 1038-28-4 dl-3-methoxy-13β-ethylgona-2,5(10)-dien-17β-ol 
• 6544-68-9 13β-ethyl-3-hydroxygona-1,3,5(10)-trien-17-one 
• 77-78-1 dimethyl sulfate 
• 3625-82-9 (+)-17β-hydroxy-13β-ethyl-3-methoxygona-1,3,5(10)-triene 
• 10051-99-7 l-3-Methoxy-13β-ethyl-gona-1,3,5(10),8-tetraen-17β-ol-hydrogensuccinat 

Downstream Products

• 848-04-4 (+)-13-ethyl-3-ethoxygona-1,3,5⁽¹⁰⁾-trien-17-one 
• 848-04-4 (-)-13-ethyl-3-ethoxygona-1,3,5⁽¹⁰⁾-trien-17-one 
• 92207-99-3 C₂₈H₃₇NO₃S 
• 92207-99-3 C₂₈H₃₇NO₃S 
• 126971-24-2 13α-Ethyl-3-methoxy-17-phenyl-1,3,5(10),14(15),16(17)-gonapentaene 
• 6544-68-9 13β-ethyl-3-hydroxygona-1,3,5(10)-trien-17-one 
• 1095-74-5 (+/-)13β-Ethyl-17α-ethynyl-17β-hydroxy-8-isogon-5(10)-en-3-one 
• 797-58-0 Norbolethone 
• 797-58-0 DL-17β-Hydroxy-13β.17α-diethyl-gon-4-en-3-on 
• 14012-72-7 13β-ethyl-18,19-dinor-17α-pregna-1,3,5(10)-trien-20-yne-3,17β-diol 
• 80904-59-2 (R)-3-Methoxy-18-methyl-16β-phenylseleninyl-1,3,5(10)-oestratrien-17α-ol 
• 80904-59-2 (S)-3-Methoxy-18-methyl-16β-phenylseleninyl-1,3,5(10)-oestratrien-17α-ol 
• 80904-58-1 (R)-3-Methoxy-18-methyl-16β-phenylsulfinyl-1,3,5(10)-oestratrien-17α-ol 
• 80904-58-1 (S)-3-Methoxy-18-methyl-16β-phenylsulfinyl-1,3,5(10)-oestratrien-17α-ol 

Relevant articles and documents

Preparation method of levonorgestrel pharmacopoeia impurity V

The invention belongs to the technical field of pharmacy, and particularly relates to a preparation method of a levonorgestrel pharmacopoeia impurity V. The preparation method comprises the steps of by taking a compound 1 as an initial raw material, carrying out aromatization reaction, methylation reaction and ethynylation reaction to prepare the levonorgestrel pharmacopoeia impurity V; the aromatization method comprises the steps of dissolving the compound 1 with an organic solvent, adding lithium bromide, controlling the temperature to be -5 to 5 DEG C, then adding copper bromide at the temperature, heating to room temperature, reacting and treating to obtain a compound 2. The product obtained by the method is high in purity and yield, avoids generation of impurities, and provides a qualified reference substance for quality control of levonorgestrel.

Copper bromide mediated A-ring dehydrogenation of 19-norsteroids

A dehydrogenation reaction applied to 19-norsteroids 1a or 1b, with copper(II) bromide in different alcohols yielded estrone alkyl ethers or 13β-ethyl-3-alkoxy gonanes along with products in which the steroid 6-position has been oxidized as aell. Use of small amounts of trialkyl orthoformates in the reaction considerably diminished the overoxidized products.

Preparative chemical methods for aromatization of 19-nor-Δ4-3-oxosteroids

Two preparative chemical methods for aromatization of 19-nor-Δ4-3-oxosteroids are described.The first method consists of an oxidative aromatization of 19-nor-Δ4-3-oxosteroids with iodine-ceric ammonium nitrate in methanol to give a mixture of 3-methoxy ring-A aromatized derivatives consisting of the desired product, the Δ9,11 derivative, the 6-oxo derivative as well as some ring-A iodinated material.Conversion of this material to a mixture of the 3-methoxy ring-A aromatized derivative and its 6-oxo derivative was achieved by catalytic hydrogenation.Finally, reduction of the 6-oxo function with triethylsilane in trifluoroacetic acid gave the 3-methoxy-17-trifluoroacetate ring-A aromatized derivative as a single product.In the second method, reaction of 19-nor-Δ4-3-oxosteroids with copper(II) bromide in acetonitrile at room temperature resulted in aromatic steroids in a single step in excellent yields.The second method was used in the first practical chemical synthesis of a 6-dehydroestrogen from a 19-nor-Δ4,6-3-oxosteroid. - Keywords: copper(II) bromide; ceric ammonium nitrate; iodine; aromatization; 19-nor-Δ4-3-oxosteroids