54024-22-5

Basic information

• Product Name: Desogestrel
• Synonyms: (17α)-13-Ethyl-11-methylene-18，19-dinorpregn-4-en-20-yn-17-ol;(8S,9S,10R,13S,14S,17R)-13-Ethyl-17-ethynyl-11-methylidene-1,2,3,6,7,8,9,10,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-ol;(17R)-13-Ethyl-11-methylene-18,19-dinorpregn-4-en-20-yn-17-ol;(8S,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-11-methylene-1,2,3,6,7,8,9,10,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-ol;Desogestrel (50 mg);(8S,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-11-Methylene-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-ol;DESTODENE;Desogestrel for system suitability, European Pharmacopoeia (EP) Reference Standard
• CAS NO: 54024-22-5
• Molecular Formula: C₂₂H₃₀O
• Molecular Weight: 310.47
• EINECS: 258-929-4
• Product Categories: Steroid and Hormone;Hormone Drugs;Intermediates & Fine Chemicals;Pharmaceuticals;Steroids
• Mol File: 54024-22-5.mol
• Article Data: 19

Chemical Properties

• Melting Point: 109-110°C
• Boiling Point: 390.62°C (rough estimate)
• Flash Point: 187.9 ºC
• Appearance: white to off-white crystalline powder
• Density: 1.0169 (rough estimate)
• Vapor Pressure: 3.92E-09mmHg at 25°C
• Refractive Index: 1.5100 (estimate)
• Storage Temp.: -20°C Freezer
• Solubility: Practically insoluble in water, very soluble in methanol, freely soluble in anhydrous ethanol and in methylene chloride.
• PKA: 13.07±0.40(Predicted)
• Merck: 14,2926
• CAS DataBase Reference: Desogestrel(CAS DataBase Reference)
• NIST Chemistry Reference: Desogestrel(54024-22-5)
• EPA Substance Registry System: Desogestrel(54024-22-5)

Safety Data

• Safety Statements: 24/25
• RIDADR: UN 3077 9 / PGIII
• WGK Germany: 3
• RTECS: JF7975000
• Hazardous Substances Data: 54024-22-5(Hazardous Substances Data)

Usage

Description

Desogestrel is a synthetic progestogen. It inhibits ovulation and prevents fertilization in rabbits and mice. Desogestrel inhibits rhodamine 123 efflux, a measure of P-glycoprotein activity, ex vivo in human lymphocytes and CD8+ T cells in a dose-dependent manner. Formulations containing desogestrel have been used as oral contraceptives and for the treatment of polycystic ovary syndrome.

Chemical Properties

White Solid

Originator

Dicromil,Organol ,W. Germany,1981

Uses

A progestogen with low androgenic potency

Manufacturing Process

A solution of 1.0 g of 11,11-methylene-18-methyl-delta4-estren-17-one in 33 ml tetrahydrofuran was added to a potassium-acetylide solution in tetrahydrofuran. After 2 hours of stirring at 0°C to 5°C the reaction mixture was acidified with 2N H2SO4and processed further.By a chromatographic treatment on silica gel and crystallization from pentane 0.7 g of 11,11-methylene-17α-ethynyl-18-methyl-δ4-estren-17β-ol with a melting point of 109°C to 110°C and an [α]D of +55°C (CHCl3) was obtained.

Therapeutic Function

Progestin

General Description

Desogestrel, (17α)-13-ethyl-11-methylene-18,19-dinorpregn-4-en-20-yn-17-ol, is a 19-nortestosterone analog with good progestin activity. Likethe other progestins, it is orally active and used in combinationwith an estrogen in oral contraceptives. Desogestrel is aprodrug that must be oxidized to the 3-one in vivo to haveprogestational action. CYPs 2C9 and 2C19 have been implicatedin the initial hydroxylation of desogestrel at C3.

Clinical Use

Desogestrel also is a prodrug and is rapidly metabolized in the intestinal mucosa and on first pass through the liver to its active metabolite, etonogestrel (3-ketodesogestrel). Following oral administration, the relative bioavailability for desogestrel is approximately 84%. Desogestrel also exhibits high selectivity for the progesterone receptor and low and rogenic activity, and it does not diminish the beneficial effects of estrogen on the lipid profile.

InChI:InChI=1/C22H30O/c1-4-21-14-15(3)20-17-9-7-6-8-16(17)10-11-18(20)19(21)12-13-22(21,23)5-2/h2,8,17-20,23H,3-4,6-7,9-14H2,1H3/t17-,18-,19-,20+,21-,22-/m0/s1

Synthetic route

C24H38O2Si → desogestrel (54024-22-5)

Conditions	Yield
With hydrogenchloride In methanol; water Solvent; Reflux;	96.5%

lithium acetylide-ethylenediamine complex (1216963-74-4) + 11-methylene-18a-homo-estr-4-en-17-one (54024-21-4) → desogestrel (54024-22-5)

Conditions	Yield
In dimethyl sulfoxide at 20℃; for 21h;	89%

11-methylene-18a-homo-estr-4-en-17-one (54024-21-4) + trimethylsilylacetylene (1066-54-2) → desogestrel (54024-22-5)

Conditions	Yield
Stage #1: trimethylsilylacetylene With n-hexyllithium In tetrahydrofuran; hexane at -5℃; for 0.5h; Stage #2: 11-methylene-18a-homo-estr-4-en-17-one In tetrahydrofuran; hexane at 0 - 5℃; for 1h;	89%

11-methylene-18a-homo-estr-4-en-17-one (54024-21-4) + acetylene (74-86-2) → desogestrel (54024-22-5)

Conditions	Yield
With lithium; ethylenediamine In tetrahydrofuran at 25℃; for 2h; continuous flow of ethyne;	85%
Stage #1: acetylene With lithium In ethylenediamine at 20℃; for 2h; Peterson olefination; Stage #2: 11-methylene-18a-homo-estr-4-en-17-one In tetrahydrofuran at 20℃; for 2h; Further stages;	83%
Stage #1: acetylene With N,N,N,N,-tetramethylethylenediamine; lithium for 2h; Stage #2: 11-methylene-18a-homo-estr-4-en-17-one In tetrahydrofuran at 20℃; for 2h; Stage #3: With hydrogenchloride; water In tetrahydrofuran	83%

C24H32OS2 (116930-33-7) → desogestrel (54024-22-5)

Conditions	Yield
With sodium In tetrahydrofuran; ammonia at -4℃; for 1h;	58%

lithium acetylide-ethylenediamine complex (1216963-74-4) + 11-methylene-18a-homo-estr-4-en-17-one (54024-21-4) → desogestrel (54024-22-5) + 16β-OH desogestrel

Conditions	Yield
In tetrahydrofuran; ethylenediamine at 10 - 20℃; for 4h;	A 0.220 g B 0.060 g

(+)-(1S,3aS,7aS)-hexahydro-1-(tert-butyldimethylsiloxy)-7a-ethyl-5-indanone (220332-76-3) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 12 steps 1: 80 percent / NaH, MeOH / tetrahydrofuran; hexane / 1 h / Heating 2: 1.) NaH, 2.) n-BuLi 3: 1.) trifluoroacetic acid, 2.) K2CO3, MeOH / 1.) CH2Cl2, 23 deg C, 24 h, 2.) 23 deg C, 1 h 4: 73 percent / imidazole / dimethylformamide / 12 h / 50 °C 5: 95 percent / LiAlH4 / tetrahydrofuran / 2 h / 23 °C 6: 85 percent / DEAD, PPh3, o-NO2PhSO2NHNH2 / tetrahydrofuran / 14 h / -40 - 23 °C 7: liq. NH3, Li / ethanol; tetrahydrofuran / 1 h / -78 °C 8: 1 M aq. HCl, 48 percent aq. HF / tetrahydrofuran / 20 h / 23 °C 9: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 10: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 11: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 12: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

(+)-(1S,3aS,7aS)-3a,4,7,7a-tetrahydro-1-(tert-butyldimethylsiloxy)-6-carbomethoxy-7a-ethyl-5-hydroxyindane (220332-77-4) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 11 steps 1: 1.) NaH, 2.) n-BuLi 2: 1.) trifluoroacetic acid, 2.) K2CO3, MeOH / 1.) CH2Cl2, 23 deg C, 24 h, 2.) 23 deg C, 1 h 3: 73 percent / imidazole / dimethylformamide / 12 h / 50 °C 4: 95 percent / LiAlH4 / tetrahydrofuran / 2 h / 23 °C 5: 85 percent / DEAD, PPh3, o-NO2PhSO2NHNH2 / tetrahydrofuran / 14 h / -40 - 23 °C 6: liq. NH3, Li / ethanol; tetrahydrofuran / 1 h / -78 °C 7: 1 M aq. HCl, 48 percent aq. HF / tetrahydrofuran / 20 h / 23 °C 8: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 9: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 10: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 11: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

(+)-13β-ethyl-11-methylenegona-4-en-17β-ol (54024-20-3) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 2: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

(+)-13β-ethyl-17β-hydroxy-11-methylenegona-4-en-3-one (220332-82-1) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 2: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 3: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 4: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

11-carbomethoxy-13-ethyl-3-methoxygona-1,3,5(10),9(11)-tetraen-17β-ol (220332-79-6) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 9 steps 1: 73 percent / imidazole / dimethylformamide / 12 h / 50 °C 2: 95 percent / LiAlH4 / tetrahydrofuran / 2 h / 23 °C 3: 85 percent / DEAD, PPh3, o-NO2PhSO2NHNH2 / tetrahydrofuran / 14 h / -40 - 23 °C 4: liq. NH3, Li / ethanol; tetrahydrofuran / 1 h / -78 °C 5: 1 M aq. HCl, 48 percent aq. HF / tetrahydrofuran / 20 h / 23 °C 6: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 7: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 8: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 9: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

(+)-13β-ethyl-3,3-ethylenedithio-11-methylenegona-4-en-17β-ol (54024-19-0) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 2: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 3: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

17β-(tert-butyldimethylsiloxy)-13-ethyl-11-methylene-3-methoxygona-1,3,5(10)-triene (161640-05-7) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 6 steps 1: liq. NH3, Li / ethanol; tetrahydrofuran / 1 h / -78 °C 2: 1 M aq. HCl, 48 percent aq. HF / tetrahydrofuran / 20 h / 23 °C 3: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 4: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 5: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 6: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

17β-(tert-butyldimethylsiloxy)-13-ethyl-11-(hydroxymethyl)-3-methoxygona-1,3,5(10),9(11)-tetraene (220332-81-0) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 7 steps 1: 85 percent / DEAD, PPh3, o-NO2PhSO2NHNH2 / tetrahydrofuran / 14 h / -40 - 23 °C 2: liq. NH3, Li / ethanol; tetrahydrofuran / 1 h / -78 °C 3: 1 M aq. HCl, 48 percent aq. HF / tetrahydrofuran / 20 h / 23 °C 4: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 5: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 6: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 7: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

(+)-(1S,3aS,4S,7aS)-3a,4,7,7a-tetrahydro-1-(tert-butyldimethylsiloxy)-6-carbomethoxy-7a-ethyl-5-hydroxy-4-(2-(3-methoxyphenyl)ethyl)indane (220332-78-5) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 10 steps 1: 1.) trifluoroacetic acid, 2.) K2CO3, MeOH / 1.) CH2Cl2, 23 deg C, 24 h, 2.) 23 deg C, 1 h 2: 73 percent / imidazole / dimethylformamide / 12 h / 50 °C 3: 95 percent / LiAlH4 / tetrahydrofuran / 2 h / 23 °C 4: 85 percent / DEAD, PPh3, o-NO2PhSO2NHNH2 / tetrahydrofuran / 14 h / -40 - 23 °C 5: liq. NH3, Li / ethanol; tetrahydrofuran / 1 h / -78 °C 6: 1 M aq. HCl, 48 percent aq. HF / tetrahydrofuran / 20 h / 23 °C 7: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 8: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 9: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 10: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

17β-(tert-butyldimethylsiloxy)-11-carbomethoxy-13-ethyl-3-methoxygona-1,3,5(10),9(11)-tetraene (220332-80-9) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 8 steps 1: 95 percent / LiAlH4 / tetrahydrofuran / 2 h / 23 °C 2: 85 percent / DEAD, PPh3, o-NO2PhSO2NHNH2 / tetrahydrofuran / 14 h / -40 - 23 °C 3: liq. NH3, Li / ethanol; tetrahydrofuran / 1 h / -78 °C 4: 1 M aq. HCl, 48 percent aq. HF / tetrahydrofuran / 20 h / 23 °C 5: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 6: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 7: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 8: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

tert-butyl-(13-ethyl-3-methoxy-11-methylene-2,6,7,8,9,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yloxy)-dimethyl-silane → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: 1 M aq. HCl, 48 percent aq. HF / tetrahydrofuran / 20 h / 23 °C 2: 100 percent / BF3*Et2O / methanol / 2 h / 23 °C 3: Li, liq. NH3 / tetrahydrofuran / 0.5 h / Heating 4: 99 percent / Dess-Martin periodinane / CH2Cl2 / 1 h / 23 °C 5: 1.) n-BuLi, 2.) Ce(III) chloride View Scheme

13β-ethyl-11-methylenegon-4-en-3,17-dione (54024-17-8) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: 98 percent / BF3*Et2O / methanol / 2.5 h / 0 - 5 °C 2: 100 percent / NaBH4 / methanol / 2 h / Ambient temperature 3: 94 percent / Na, liq. NH3 / tetrahydrofuran / 0.5 h / -50 - -45 °C 4: 82 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 5: 72 percent / n-C4H9Br, Li / tetrahydrofuran; diethyl ether / 1.) -10 deg C, 2 h; -5 deg C, 3 h, 2.) -5 deg C, 3 h View Scheme
Multi-step reaction with 3 steps 1: 91 percent / BF3*Et2O / tetrahydrofuran / 2.75 h / Heating 2: t-BuOK / tetrahydrofuran / 2 h / -20 - -15 °C 3: 58 percent / Na / liquid ammonia; tetrahydrofuran / 1 h / -4 °C View Scheme
Multi-step reaction with 5 steps 1.1: hydrogenchloride / 1,2-dimethoxyethane; 1,4-dioxane / -10 °C 1.2: 3 h / -15 - -10 °C 1.3: 0.67 h 2.1: sodium tetrahydroborate; water / ethanol / 0 - 20 °C 3.1: zinc; acetic acid / water / 12 h / 20 °C 4.1: sodium carbonate / water; tetrahydrofuran; dichloromethane / 0.17 h / 20 °C 4.2: 20 °C 5.1: ethylenediamine; lithium / tetrahydrofuran / 5 h / 30 - 50 °C View Scheme

13-ethyl-11-methylenegon-4-ene-3,17-dione cyclic 3-(1,2-ethanediyl dithioacetal) (54024-18-9) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 100 percent / NaBH4 / methanol / 2 h / Ambient temperature 2: 94 percent / Na, liq. NH3 / tetrahydrofuran / 0.5 h / -50 - -45 °C 3: 82 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 4: 72 percent / n-C4H9Br, Li / tetrahydrofuran; diethyl ether / 1.) -10 deg C, 2 h; -5 deg C, 3 h, 2.) -5 deg C, 3 h View Scheme
Multi-step reaction with 2 steps 1: t-BuOK / tetrahydrofuran / 2 h / -20 - -15 °C 2: 58 percent / Na / liquid ammonia; tetrahydrofuran / 1 h / -4 °C View Scheme

13β-ethyl-11α-hydroxygon-5-ene-3,17-dione (53067-82-6) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 9 steps 1: 94 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 2: 79 percent / HC(OEt)3, p-TsOH*H2O / CH2Cl2 / 7 h / Heating 3: 88 percent / benzene; diethyl ether / 3 h / 10 - 15 °C 4: 74 percent / p-TsOH*H2O / formic acid / 7 h / 50 - 60 °C 5: 98 percent / BF3*Et2O / methanol / 2.5 h / 0 - 5 °C 6: 100 percent / NaBH4 / methanol / 2 h / Ambient temperature 7: 94 percent / Na, liq. NH3 / tetrahydrofuran / 0.5 h / -50 - -45 °C 8: 82 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 9: 72 percent / n-C4H9Br, Li / tetrahydrofuran; diethyl ether / 1.) -10 deg C, 2 h; -5 deg C, 3 h, 2.) -5 deg C, 3 h View Scheme

13β-ethyl-gona-5-ene-3,11,17-trione-3,17-diethylene ketal (196716-43-5) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 7 steps 1: 88 percent / benzene; diethyl ether / 3 h / 10 - 15 °C 2: 74 percent / p-TsOH*H2O / formic acid / 7 h / 50 - 60 °C 3: 98 percent / BF3*Et2O / methanol / 2.5 h / 0 - 5 °C 4: 100 percent / NaBH4 / methanol / 2 h / Ambient temperature 5: 94 percent / Na, liq. NH3 / tetrahydrofuran / 0.5 h / -50 - -45 °C 6: 82 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 7: 72 percent / n-C4H9Br, Li / tetrahydrofuran; diethyl ether / 1.) -10 deg C, 2 h; -5 deg C, 3 h, 2.) -5 deg C, 3 h View Scheme

18-methyl-estra-4-en-3,11,17-trione (100071-90-7) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 8 steps 1: 79 percent / HC(OEt)3, p-TsOH*H2O / CH2Cl2 / 7 h / Heating 2: 88 percent / benzene; diethyl ether / 3 h / 10 - 15 °C 3: 74 percent / p-TsOH*H2O / formic acid / 7 h / 50 - 60 °C 4: 98 percent / BF3*Et2O / methanol / 2.5 h / 0 - 5 °C 5: 100 percent / NaBH4 / methanol / 2 h / Ambient temperature 6: 94 percent / Na, liq. NH3 / tetrahydrofuran / 0.5 h / -50 - -45 °C 7: 82 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 8: 72 percent / n-C4H9Br, Li / tetrahydrofuran; diethyl ether / 1.) -10 deg C, 2 h; -5 deg C, 3 h, 2.) -5 deg C, 3 h View Scheme

D-13β-Ethyl-11-methylenegon-4-en-17α-ol (196716-46-8) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 2: 72 percent / n-C4H9Br, Li / tetrahydrofuran; diethyl ether / 1.) -10 deg C, 2 h; -5 deg C, 3 h, 2.) -5 deg C, 3 h View Scheme

D-13β-Ethyl-3,3-ethylenedithio-11-methylenegon-4-ene-17α-ol (196716-45-7) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 94 percent / Na, liq. NH3 / tetrahydrofuran / 0.5 h / -50 - -45 °C 2: 82 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 3: 72 percent / n-C4H9Br, Li / tetrahydrofuran; diethyl ether / 1.) -10 deg C, 2 h; -5 deg C, 3 h, 2.) -5 deg C, 3 h View Scheme

D-13β-Ethyl-11β-hydroxy-11α-methylgon-5-ene-3,11-dione-3,17-diethylene ketal (196716-44-6) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 6 steps 1: 74 percent / p-TsOH*H2O / formic acid / 7 h / 50 - 60 °C 2: 98 percent / BF3*Et2O / methanol / 2.5 h / 0 - 5 °C 3: 100 percent / NaBH4 / methanol / 2 h / Ambient temperature 4: 94 percent / Na, liq. NH3 / tetrahydrofuran / 0.5 h / -50 - -45 °C 5: 82 percent / Jones' reagent / acetone / 0.25 h / -15 - -10 °C 6: 72 percent / n-C4H9Br, Li / tetrahydrofuran; diethyl ether / 1.) -10 deg C, 2 h; -5 deg C, 3 h, 2.) -5 deg C, 3 h View Scheme

13-ethyl-gona-4-ene-11α,17β-diol (160683-92-1) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 5 steps 1: 85 percent / SO3 pyridine complex / triethylamine; dimethylsulfoxide / 3 h / Ambient temperature 2: 85 percent / triethylorthoformate, p-toluenesulfonic acid hydrate / 3 h / 40 °C 3: 85 percent / NaH / dimethylsulfoxide; toluene / 12 h / 80 °C / sonification 4: p-toluenesulfonic acid hydrate / acetone / 12 h / Ambient temperature 5: 85 percent / Li, ethylenediamine / tetrahydrofuran / 2 h / 25 °C / continuous flow of ethyne View Scheme

18a-homo-estr-4-ene-11,17-dione (160683-93-2) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 85 percent / triethylorthoformate, p-toluenesulfonic acid hydrate / 3 h / 40 °C 2: 85 percent / NaH / dimethylsulfoxide; toluene / 12 h / 80 °C / sonification 3: p-toluenesulfonic acid hydrate / acetone / 12 h / Ambient temperature 4: 85 percent / Li, ethylenediamine / tetrahydrofuran / 2 h / 25 °C / continuous flow of ethyne View Scheme
Multi-step reaction with 3 steps 1: n-butyllithium / tetrahydrofuran; hexane / 15 - 30 °C 2: tetrahydrofuran; hexane / Reflux 3: hydrogenchloride / methanol; water / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: tetrahydrofuran / 1.5 h / 0 - 10 °C 1.2: 1.5 h / 25 °C 2.1: n-hexyllithium / tetrahydrofuran; hexane / 0.5 h / -5 °C 2.2: 1 h / 0 - 5 °C View Scheme

3-methoxy-18a-homo-estra-2,5(10)-diene-11α,17β-diol (160683-85-2) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 8 steps 1: 92 percent / HCl / acetone; H2O 2: boron trifluoride diethyl ether / methanol / 1 h / Ambient temperature 3: 87 percent / Li, ethylamine / tetrahydrofuran / 0.5 h / -35 - -30 °C 4: 85 percent / SO3 pyridine complex / triethylamine; dimethylsulfoxide / 3 h / Ambient temperature 5: 85 percent / triethylorthoformate, p-toluenesulfonic acid hydrate / 3 h / 40 °C 6: 85 percent / NaH / dimethylsulfoxide; toluene / 12 h / 80 °C / sonification 7: p-toluenesulfonic acid hydrate / acetone / 12 h / Ambient temperature 8: 85 percent / Li, ethylenediamine / tetrahydrofuran / 2 h / 25 °C / continuous flow of ethyne View Scheme

3,3-ethylenedithio-18a-homo-estr-4-ene-11α,17β-diol (160683-91-0) → desogestrel (54024-22-5)

Conditions

Yield

Multi-step reaction with 6 steps 1: 87 percent / Li, ethylamine / tetrahydrofuran / 0.5 h / -35 - -30 °C 2: 85 percent / SO3 pyridine complex / triethylamine; dimethylsulfoxide / 3 h / Ambient temperature 3: 85 percent / triethylorthoformate, p-toluenesulfonic acid hydrate / 3 h / 40 °C 4: 85 percent / NaH / dimethylsulfoxide; toluene / 12 h / 80 °C / sonification 5: p-toluenesulfonic acid hydrate / acetone / 12 h / Ambient temperature 6: 85 percent / Li, ethylenediamine / tetrahydrofuran / 2 h / 25 °C / continuous flow of ethyne View Scheme

11-methylene-17-<(2,2-dimethyl)propane-1,3-dioxy>-18a-homo-estr-4-ene (160683-95-4) → desogestrel (54024-22-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: p-toluenesulfonic acid hydrate / acetone / 12 h / Ambient temperature 2: 85 percent / Li, ethylenediamine / tetrahydrofuran / 2 h / 25 °C / continuous flow of ethyne View Scheme

carbon monoxide (201230-82-2) + 2-(2-(1-phenylethylidene)hydrazinyl)pyridine + desogestrel (54024-22-5) → 2-{(8S,9S,10R,13S,14S,17S)-13-ethyl-17-hydroxy-11-methylene-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl}-4H-pyrido[1,2-a]pyrimidin-4-one

Conditions	Yield
With dimanganese decacarbonyl In toluene at 100℃; under 760.051 Torr; for 16h; Schlenk technique; Sealed tube;	86%

Dimethylphenylsilane (766-77-8) + desogestrel (54024-22-5) → (8S,9S,10R,13S,14S,17S)-17-((dimethyl(phenyl)silyl)ethynyl)-13-ethyl-11-methylene-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-ol

Conditions	Yield
With potassium hydroxide In 1,2-dimethoxyethane at 45℃; for 48h;	60%

desogestrel (54024-22-5) + allyl bromide (106-95-6) → 17-O-allyldesogestrel

Conditions	Yield
Stage #1: desogestrel With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 1.5h; Inert atmosphere; Stage #2: allyl bromide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 16h; Inert atmosphere;	58%

desogestrel (54024-22-5) → 17α-Bromethinyl-18-methyl-11-methylen-4-oestren-17β-ol (91781-33-8)

Conditions	Yield
With N-Bromosuccinimide; silver nitrate In acetone for 0.75h; Ambient temperature;	51%

acetic anhydride (108-24-7) + desogestrel (54024-22-5) → Acetic acid (8S,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-11-methylene-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester (160683-96-5)

Conditions	Yield
With perchloric acid In toluene for 1h; Ambient temperature;

Upstream product

• 1216963-74-4 lithium acetylide-ethylenediamine complex 
• 54024-21-4 11-methylene-18a-homo-estr-4-en-17-one 
• 170901-07-2 C₁₉H₂₆O₃ 
• 1066-54-2 trimethylsilylacetylene 
• 163918-37-4 17,17-ethylenedioxy-18a-homo-estr-4-en-11-one 
• 59860-72-9 3,3:17,17-bis[1,2-ethenediylbis(oxy)]-11β-hydroxyestr-5-en-18-oic acid γ-lactone 
• 100071-89-4 18a-homoestr-5-ene-3,11,17-trione cyclic 3,17-bis(1,2-ethanediyl acetal) 
• 56294-43-0 13-ethyl-11-methylenegon-5-ene-3,17-dione cyclic bis(1,2-ethanediyl acetal) 
• 59017-10-6 13-ethyl-11β-hydroxygon-5-ene-3,17-dione cyclic bis(1,2-ethanediyl acetal) 
• 7370-08-3 11α,17β-Dihydroxy-18a-homo-estr-4-en-3-one 
• 160683-94-3 17,17-<(2,2-dimethyl)propane-1,3-dioxy>-18a-homo-estr-4-en-11-one 

Downstream Products

• 54048-10-1 etonogestrel 

Relevant articles and documents

Base promoted air oxidation of 13β-ethyl-11-methylenegon-4-en-17-one

The structure of 13-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-16β,17-diol (3, 16β-OH desogestrel), a by-product obtained in the last step of the synthesis of desogestrel (1) by reaction of monolithium acetylide-ethylenediamine complex with 13β-e

Intermediate used for synthesis of desogestrel, and preparation method and application thereof

The invention discloses an intermediate used for synthesis of desogestrel, and a preparation method and application thereof. The intermediate has a general chemical structural formula as described in the specification, wherein a substituting group R is selected from the group consisting of hydrogen, methyl or ethyl. The intermediate is prepared by subjecting a compound as shown in a formula 2 to selective protection reaction for a 3-carbonyl group by using dihydric alcohol, wherein the dihydric alcohol has a chemical structural formula as described in the specification, wherein R is selected from the group consisting of hydrogen, methyl or ethyl; and a reaction formula of the dihydric alcohol is described in the specification. The method for the synthesis of the desogestrel by employing the intermediate comprises a reaction route as described in the specification.

Desogestrel preparation method and midbody compound

The invention relates to a novel steroidal compound and application of the novel steroidal compound in a desogestrel preparation process. The novel compound easy to separate is obtained through 17-bit selective ethynylation of 13beta-ethyl pregnane-4, 5-alkene-11, 17-diketone. When the compound is used for preparing desogestrel, simplicity and convenience in operation are achieved, and yield is high.