875573-66-3

Basic information

• Product Name: (7a,17b)-7-(9-Bromononyl)-estra-1,3,5(10)-triene-3,17-diol 17-acetate
• Synonyms: (7a,17b)-7-(9-Bromononyl)-estra-1,3,5(10)-triene-3,17-diol 17-acetate;Estra-1,3,5(10)-triene-3,17-diol,7-(9-broMononyl)-,17-acetate,(7a,17b)-;(7R,8R,9S,13S,14S,17S)-7-(9-Bromononyl)-3-hydroxy-13-methyl-7,8,9,11, 12,13,14,15,16,17-decahydro;(7a,17b)-7-(9-BroMononyl)-estra-1,3,5(1)-triene-3,17-diol 17-acetate;(7R,8R,9S,13S,14S,17S)-7-(9-BroMononyl)-3-hydroxy-13-Methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yl acetate;Fulvestrant Intermediates-5(N-3);(7R,8R,9S,13S,14S,17S)-7-(9-Bromononyl)-3-hydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahyd
• CAS NO: 875573-66-3
• Molecular Formula: C₂₉H₄₃BrO₃
• Molecular Weight: 519.55
• Mol File: 875573-66-3.mol

Chemical Properties

• Boiling Point: 593.274 °C at 760 mmHg
• Flash Point: 312.601 °C
• Appearance: /
• Density: 1.22
• Storage Temp.: 2-8°C
• PKA: 10.26±0.70(Predicted)
• CAS DataBase Reference: (7a,17b)-7-(9-Bromononyl)-estra-1,3,5(10)-triene-3,17-diol 17-acetate(CAS DataBase Reference)
• NIST Chemistry Reference: (7a,17b)-7-(9-Bromononyl)-estra-1,3,5(10)-triene-3,17-diol 17-acetate(875573-66-3)
• EPA Substance Registry System: (7a,17b)-7-(9-Bromononyl)-estra-1,3,5(10)-triene-3,17-diol 17-acetate(875573-66-3)

Safety Data

• Hazardous Substances Data: 875573-66-3(Hazardous Substances Data)

Usage

Uses

Used in Menopause Management:
Tibolone is used as a hormone replacement therapy agent for managing menopausal symptoms in women. It helps alleviate symptoms such as hot flashes and vaginal dryness, providing relief and improving the quality of life for menopausal women.
Used in Bone Health:
Tibolone is used as a bone health supplement to prevent bone loss and reduce the risk of fractures in postmenopausal women. Its estrogenic effects help maintain bone density, promoting overall skeletal health.
Used in Mood Regulation:
Tibolone is used as a mood enhancer in menopausal women, as it has been found to have beneficial effects on mood and emotional well-being. Its androgenic properties may contribute to improved mood stability.
Used in Sexual Function Improvement:
Tibolone is used to improve sexual function in menopausal women. Its estrogenic and androgenic properties help address issues related to sexual desire, arousal, and satisfaction, enhancing overall sexual health and well-being.

Synthetic route

(+)-3-oxo-(7α)-[9-bromononyl]estr-4-en-17β-ylacetate (875573-63-0) → (+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate (875573-66-3)

Conditions	Yield
With lithium bromide; copper(ll) bromide In acetonitrile at 20℃; for 2h; Inert atmosphere; Schlenk technique;	77%
With lithium bromide; copper(ll) bromide In acetonitrile at 20℃; for 7h;
With lithium bromide; copper(ll) bromide In acetonitrile at 20℃; for 3h; Large scale;

9-bromo-1-nonene (89359-54-6) → (+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate (875573-66-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: Schwartz's reagent / dichloromethane / 0.33 h / 20 °C / Inert atmosphere; Schlenk technique 1.2: 0.17 h / 20 °C / Inert atmosphere; Schlenk technique 1.3: 20 °C / Inert atmosphere; Schlenk technique 2.1: lithium bromide; copper(ll) bromide / acetonitrile / 2 h / 20 °C / Inert atmosphere; Schlenk technique View Scheme

6-dehydro-19-nortestosterone acetate (2590-41-2) → (+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate (875573-66-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: Schwartz's reagent / dichloromethane / 0.33 h / 20 °C / Inert atmosphere; Schlenk technique 1.2: 0.17 h / 20 °C / Inert atmosphere; Schlenk technique 1.3: 20 °C / Inert atmosphere; Schlenk technique 2.1: lithium bromide; copper(ll) bromide / acetonitrile / 2 h / 20 °C / Inert atmosphere; Schlenk technique View Scheme

C30H46O6S → (+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate (875573-66-3)

Conditions	Yield
Stage #1: C30H46O6S With hydrogen bromide In acetonitrile at 20 - 25℃; for 1h; Stage #2: With lithium hydroxide In water; acetonitrile at 50 - 60℃; for 2h; Reagent/catalyst; Temperature;	10.1 g

9-bromononan-1-ol (55362-80-6) → (+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate (875573-66-3)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: 1H-imidazole; formaldehyd / toluene / 5 h / 0 - 5 °C / Large scale 2.1: magnesium / tetrahydrofuran / 4.33 h / 50 - 65 °C / Inert atmosphere; Large scale 2.2: 1 h / -30 - -15 °C / Inert atmosphere; Large scale 3.1: triphenylphosphine; bromine / dichloromethane / 3 h / -10 - 25 °C / Inert atmosphere; Large scale 4.1: copper(ll) bromide; lithium bromide / acetonitrile / 3 h / 20 °C / Large scale View Scheme

ω-bromononanyl dimethyl-tert-butylsilyl ether (149051-24-1) → (+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate (875573-66-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: magnesium / tetrahydrofuran / 4.33 h / 50 - 65 °C / Inert atmosphere; Large scale 1.2: 1 h / -30 - -15 °C / Inert atmosphere; Large scale 2.1: triphenylphosphine; bromine / dichloromethane / 3 h / -10 - 25 °C / Inert atmosphere; Large scale 3.1: copper(ll) bromide; lithium bromide / acetonitrile / 3 h / 20 °C / Large scale View Scheme

7α-[9-(tert-butyldimethylsiloxy)nonyl]estr-4-ene-17β-acetate-3-one (875573-60-7) → (+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate (875573-66-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: triphenylphosphine; bromine / dichloromethane / 3 h / -10 - 25 °C / Inert atmosphere; Large scale 2: copper(ll) bromide; lithium bromide / acetonitrile / 3 h / 20 °C / Large scale View Scheme

(+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate (875573-66-3) + C6H9F5N2S*ClH → (+)-(7α)-[9-(4,4,5,5,5-pentafluoropentylsulfanyl)nonyl]estra-1,3,5(10)-triene-3,17β-diol (153004-31-0)

Conditions	Yield
With potassium hydroxide In water; N,N-dimethyl-formamide at 0 - 40℃; for 3.5h; Reagent/catalyst; Solvent;	90%
Stage #1: (+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate; C6H9F5N2S*ClH With potassium hydroxide In N,N-dimethyl-formamide at 0 - 10℃; for 1.5h; Stage #2: In water; N,N-dimethyl-formamide at 10 - 40℃; for 2h; Stage #3: With acetic acid In water; ethyl acetate; N,N-dimethyl-formamide for 0.166667h; Reagent/catalyst; Solvent;	90%

(+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate (875573-66-3) + C6H9F5N2S*ClH → 17-O-acetyl-S-deoxo-fulvestrant (875573-69-6)

Conditions	Yield
Stage #1: (+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate; C6H9F5N2S*ClH With potassium hydroxide In N,N-dimethyl-formamide at 0 - 10℃; for 1.5h; Stage #2: With acetic acid In ethyl acetate; N,N-dimethyl-formamide for 0.166667h;	85%

(+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate (875573-66-3) + 4,4,5,5,5-pentafluoro-1-pentanethiol (148757-88-4) → 17-O-acetyl-S-deoxo-fulvestrant (875573-69-6)

Conditions	Yield
With sodium hydroxide In N,N-dimethyl acetamide; water at 20℃; for 0.6h; Product distribution / selectivity;

(+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate (875573-66-3) + thiourea (17356-08-0) → BrH*C29H46N2O3S

Conditions	Yield
In isopropyl alcohol; toluene at 80℃; for 16h;

(+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate (875573-66-3) → 7α-(9-bromononyl)estra-1,3,5(10)-triene-3,17β-diol (875573-67-4)

Conditions	Yield
With methanol; water; hydrogen bromide at 60℃; for 0.8h;
With hydrogen bromide In methanol at 60℃; for 2h; Temperature;	4.3 g
With hydrogen bromide In methanol for 3h; Reflux; Large scale;	4.8 kg

(+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate (875573-66-3) + 4,4,5,5,5-pentafluoro-1-pentanethiol (148757-88-4) → (+)-(7α)-[9-(4,4,5,5,5-pentafluoropentylsulfanyl)nonyl]estra-1,3,5(10)-triene-3,17β-diol (153004-31-0)

Conditions	Yield
In methanol at 40℃; for 2h; Inert atmosphere; Schlenk technique;	596 mg

(+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate (875573-66-3) + 4,4,5,5,5-pentafluoro-1-pentanethiol (148757-88-4) → fulvestrant (129453-61-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 2 h / 40 °C / Inert atmosphere; Schlenk technique 2: dihydrogen peroxide; acetic acid / water; ethyl acetate / 4 h / 40 °C / Inert atmosphere; Schlenk technique View Scheme

(+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate (875573-66-3) → (+)-(7α)-[9-(4,4,5,5,5-pentafluoropentylsulfanyl)nonyl]estra-1,3,5(10)-triene-3,17β-diol (153004-31-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen bromide / methanol / 3 h / Reflux; Large scale 2: sodium hydroxide / N,N-dimethyl-formamide; water / 1.5 h / 0 - 15 °C / Large scale View Scheme

(+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate (875573-66-3) → fulvestrant (129453-61-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogen bromide / methanol / 3 h / Reflux; Large scale 2: sodium hydroxide / N,N-dimethyl-formamide; water / 1.5 h / 0 - 15 °C / Large scale 3: acetic acid; dihydrogen peroxide / ethyl acetate / 8 h / 20 - 30 °C / Large scale View Scheme

Upstream product

• 89359-54-6 9-bromo-1-nonene 
• 2590-41-2 6-dehydro-19-nortestosterone acetate 
• 55362-80-6 9-bromononan-1-ol 
• 149051-24-1 ω-bromononanyl dimethyl-tert-butylsilyl ether 
• 875573-60-7 7α-[9-(tert-butyldimethylsiloxy)nonyl]estr-4-ene-17β-acetate-3-one 
• 875573-63-0 (+)-3-oxo-(7α)-[9-bromononyl]estr-4-en-17β-ylacetate 

Downstream Products

• 875573-69-6 17-O-acetyl-S-deoxo-fulvestrant 
• 875573-67-4 7α-(9-bromononyl)estra-1,3,5(10)-triene-3,17β-diol 
• 153004-31-0 (+)-(7α)-[9-(4,4,5,5,5-pentafluoropentylsulfanyl)nonyl]estra-1,3,5(10)-triene-3,17β-diol 
• 129453-61-8 fulvestrant 

Relevant articles and documents

Impurity control method of fulvestrant

The invention belongs to the field of pharmaceutical chemicals, and relates to a fulvestrant impurity control method, which is characterized in that from the introduction of chiral carbon to the synthesis of a fulvestrant intermediate compound represented by a formula VII-1, multi-step and step-by-step control is performed on 7beta isomer impurities, so that the 7beta isomer content of the VII-1 compound is between 0.1% and 0.3%, and finally the qualified fulvestrant bulk drug with stable quality is prepared. The impurity control method is simple to operate, low in production cost and high intotal yield, and can be applied to large-scale industrial production.

Compounding method for fulvestrant midbody

The invention relates to a preparation method for a fulvestrant midbody. The method specifically comprises the following steps: adding pyridinium bromide perbromide into a compound shown as formula I and dehydrogenizing, and then adding lithium hydroxide into a reaction liquid and reacting, thereby acquiring a compound shown as formula II. According to the invention, pyridinium bromide perbromide is used as a dehydrogenizing agent, one-pot continuous reaction is adopted for realizing dehydrogenizing and bromination two-step reaction, the production technology is simplified, the product yield and quality are promoted, the use of heavy metal reagents, such as copper, is avoided and the environmental pollution is reduced.

An alternative synthesis of the breast cancer drug fulvestrant (Faslodex): catalyst control over C-C bond formation

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