875573-67-4

Basic information

• Product Name: (7a,17b)-7-(9-Bromononyl)estra-1,3,5(10)-triene-3,17-diol
• Synonyms: Estra-1,3,5(10)-triene-3,17-diol, 7-(9-broMononyl)-, (7a,17b)- (9CI);Fulvestrant Intermediates--5-1(N-3-1);Estra-1,3,5(10)-triene-3,17-diol, 7-(9-bromononyl)-, (7α,17β)-;(7A,17BETA)-7-(9-BROMONONYL)ESTRA-1,3,5(10)-TRIENE-3,17-DIOL;(7α,17β)-7-(9-bromononyl)estra-1,3,5(10)-triene-3,17-diol;(7a,17b)-7-(9-Bromononyl)estra-1,3,5(10)-triene-3,17-diol;Fulvestrant interMediate N-2(1);(7R,8R,9S,13S,14S,17S)-7-(9-bromononyl)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
• CAS NO: 875573-67-4
• Molecular Formula: C₂₇H₄₁BrO₂
• Molecular Weight: 477.52
• EINECS: 1592732-453-0
• Mol File: 875573-67-4.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 586.1±50.0 °C(Predicted)
• Appearance: Off-white crystal powder
• Density: 1.196
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 10.27±0.70(Predicted)
• CAS DataBase Reference: (7a,17b)-7-(9-Bromononyl)estra-1,3,5(10)-triene-3,17-diol(CAS DataBase Reference)
• NIST Chemistry Reference: (7a,17b)-7-(9-Bromononyl)estra-1,3,5(10)-triene-3,17-diol(875573-67-4)
• EPA Substance Registry System: (7a,17b)-7-(9-Bromononyl)estra-1,3,5(10)-triene-3,17-diol(875573-67-4)

Safety Data

• Hazardous Substances Data: 875573-67-4(Hazardous Substances Data)

Usage

Uses

(7a,17b)-7-(9-Bromononyl)estra-1,3,5(10)-triene-3,17-diol is used in the synthetic preparation of 7α-alkylated 19-norsteroids.

Synthetic route

(+)-(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

9-bromononan-1-ol (55362-80-6) → 7α-(9-bromononyl)estra-1,3,5(10)-triene-3,17β-diol (875573-67-4)

Conditions

Yield

Multi-step reaction with 5 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 5.1: hydrogen bromide / methanol / 3 h / Reflux; Large scale View Scheme

ω-bromononanyl dimethyl-tert-butylsilyl ether (149051-24-1) → 7α-(9-bromononyl)estra-1,3,5(10)-triene-3,17β-diol (875573-67-4)

Conditions

Yield

Multi-step reaction with 4 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 4.1: hydrogen bromide / methanol / 3 h / Reflux; 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-3,17β-diol (875573-67-4)

Conditions	Yield
Multi-step reaction with 3 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 3: hydrogen bromide / methanol / 3 h / Reflux; Large scale View Scheme

(+)-3-oxo-(7α)-[9-bromononyl]estr-4-en-17β-ylacetate (875573-63-0) → 7α-(9-bromononyl)estra-1,3,5(10)-triene-3,17β-diol (875573-67-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: copper(ll) bromide; lithium bromide / acetonitrile / 3 h / 20 °C / Large scale 2: hydrogen bromide / methanol / 3 h / Reflux; Large scale View Scheme

7α-(9-bromononyl)estra-1,3,5(10)-triene-3,17β-diol (875573-67-4) + S-(4,4,5,5,5-pentafluoropentyl)isothiourea p-nitrobenzenesulfonate → (+)-(7α)-[9-(4,4,5,5,5-pentafluoropentylsulfanyl)nonyl]estra-1,3,5(10)-triene-3,17β-diol (153004-31-0)

Conditions	Yield
With sodium hydroxide In water; N,N-dimethyl-formamide at 0 - 15℃; for 1.5h; Large scale;	100%

7α-(9-bromononyl)estra-1,3,5(10)-triene-3,17β-diol (875573-67-4) + 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
With sodium hydroxide In N,N-dimethyl acetamide; water for 1h; Product distribution / selectivity;

7α-(9-bromononyl)estra-1,3,5(10)-triene-3,17β-diol (875573-67-4) + thiourea (17356-08-0) → BrH*C28H44N2O2S

Conditions	Yield
In N,N-dimethyl acetamide at 80℃; for 16h;

Upstream product

• 875573-63-0 (+)-3-oxo-(7α)-[9-bromononyl]estr-4-en-17β-ylacetate 
• 875573-60-7 7α-[9-(tert-butyldimethylsiloxy)nonyl]estr-4-ene-17β-acetate-3-one 
• 149051-24-1 ω-bromononanyl dimethyl-tert-butylsilyl ether 
• 55362-80-6 9-bromononan-1-ol 
• 875573-66-3 (+)-(7α)-[9-bromononyl]estra-1,3,5(10)-triene-3-ol-17β-yl acetate 

Downstream Products

• 153004-31-0 (+)-(7α)-[9-(4,4,5,5,5-pentafluoropentylsulfanyl)nonyl]estra-1,3,5(10)-triene-3,17β-diol 

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.

Process for the preparation of 7alpha-alkylated 19-norsteroids

Processes useful in the preparation of pharmaceutical compounds such as fulvestrant and processes for the preparation of fulvestrant.