7599-79-3

Basic information

• Product Name: trans-clomifene citrate
• Synonyms: trans-clomifene citrate;Enclomiphene citrate;trans-Clomiphene citrate;Triethylamine, 2-(p-(2-chloro-1,2-diphenylvinyl)phenoxy)-, citrate, (E)-;Unii-J303A6U9Y6;(E)-Clomiphene citrate;Androxal;Clomiphene B citrate
• CAS NO: 7599-79-3
• Molecular Formula: C₆H₈O₇*C₂₆H₂₈ClNO
• Molecular Weight: 598.08314
• Product Categories: Amines, Aromatics, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 7599-79-3.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 509°Cat760mmHg
• Flash Point: 261.6°C
• Appearance: /
• Density: g/cm³
• Storage Temp.: Amber Vial, -20°C Freezer
• Solubility: DMSO (Slightly), Ethyl Acetate (Slightly, Heated, Sonicated), Methanol (Slightly
• Stability: Light Sensitive
• CAS DataBase Reference: trans-clomifene citrate(CAS DataBase Reference)
• NIST Chemistry Reference: trans-clomifene citrate(7599-79-3)
• EPA Substance Registry System: trans-clomifene citrate(7599-79-3)

Safety Data

• Hazardous Substances Data: 7599-79-3(Hazardous Substances Data)

Usage

Uses

trans-Clomiphene Citrate, stereoisomer of Clomiphene Citrate (C587025), a synthetic estrogen agonist-antagonist. Gonad-stimulating principle.

Synthetic route

ethanamine, 2-[4-[(1E)-2-chloro-1,2-diphenyl ethenyl]phenoxy]-N,N-diethyl-, (±)-1,1‘-binaphthyl-2,2’-diylhydrogenphosphate + citric acid (77-92-9) → clomiphene citrate (7599-79-3)

Conditions	Yield
Stage #1: ethanamine, 2-[4-[(1E)-2-chloro-1,2-diphenyl ethenyl]phenoxy]-N,N-diethyl-, (±)-1,1‘-binaphthyl-2,2’-diylhydrogenphosphate With sodium hydroxide In water; toluene at 20℃; for 2h; Stage #2: citric acid In acetone at 0 - 50℃; for 2h;	97.07 g
Stage #1: ethanamine, 2-[4-[(1E)-2-chloro-1,2-diphenyl ethenyl]phenoxy]-N,N-diethyl-, (±)-1,1‘-binaphthyl-2,2’-diylhydrogenphosphate With ammonia In ethyl acetate Stage #2: citric acid In ethanol; ethyl acetate at 20℃; for 1h;
Stage #1: ethanamine, 2-[4-[(1E)-2-chloro-1,2-diphenyl ethenyl]phenoxy]-N,N-diethyl-, (±)-1,1‘-binaphthyl-2,2’-diylhydrogenphosphate With ammonium hydroxide In tert-butyl methyl ether; water; isopropyl alcohol for 1h; Stage #2: citric acid In ethanol; water at 60 - 65℃;	269 g

1-{4-[2-(diethylamino)ethoxy]phenyl}-1,2-diphenylethanol → clomiphene citrate (7599-79-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: hydrogenchloride / toluene / Dean-Stark; Reflux 2.1: acetic acid; 1,3-dichloro-5,5-dimethylhydantoin / toluene / 2 h / 60 °C 2.2: 4.5 h / 0 °C / Heating 3.1: methanol / 1 h / 20 - 45 °C 4.1: sodium hydroxide / toluene; water / 2 h / 20 °C 4.2: 2 h / 0 - 50 °C View Scheme

clomifene citrate (50-41-9) → clomiphene citrate (7599-79-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: methanol / 1 h / 20 - 45 °C 2.1: sodium hydroxide / toluene; water / 2 h / 20 °C 2.2: 2 h / 0 - 50 °C View Scheme

2-{4-(1,2-diphenylethenyl)phenoxy}-N,N-diethylethanamine hydrochloride (19957-52-9) → clomiphene citrate (7599-79-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: acetic acid; 1,3-dichloro-5,5-dimethylhydantoin / toluene / 2 h / 60 °C 1.2: 4.5 h / 0 °C / Heating 2.1: methanol / 1 h / 20 - 45 °C 3.1: sodium hydroxide / toluene; water / 2 h / 20 °C 3.2: 2 h / 0 - 50 °C View Scheme

1-{4-[2-(diethylamino)ethoxy]phenyl}-1,2-diphenylethanol (73404-00-9) → clomiphene citrate (7599-79-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sulfuric acid / dichloromethane / 1 h / 0 - 20 °C 2.1: N-chloro-succinimide / dichloromethane / 32 h / 20 °C 2.2: 0.5 h / 20 °C / pH 8 - 9 3.1: methanol / 2 h / 20 °C 4.1: ammonia / ethyl acetate 4.2: 1 h / 20 °C View Scheme

clomiphene (911-45-5) → clomiphene citrate (7599-79-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: methanol / 2 h / 20 °C 2.1: ammonia / ethyl acetate 2.2: 1 h / 20 °C View Scheme

2-{4-[(Z)-1,2-diphenylvinyl]phenoxy}-N,N-diethylethanaminium hydrogen sulfate → clomiphene citrate (7599-79-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: N-chloro-succinimide / dichloromethane / 32 h / 20 °C 1.2: 0.5 h / 20 °C / pH 8 - 9 2.1: methanol / 2 h / 20 °C 3.1: ammonia / ethyl acetate 3.2: 1 h / 20 °C View Scheme

clomiphene (911-45-5, 15690-55-8, 15690-57-0) + citric acid (77-92-9) → clomiphene citrate (7599-79-3)

Conditions	Yield
In ethanol; water at 65℃; Solvent;	20.2 g

clomiphene citrate (7599-79-3) → clomiphene (911-45-5, 15690-55-8, 15690-57-0)

Conditions	Yield
With sodium hydroxide In ethyl acetate for 0.5h;	99%

clomiphene citrate (7599-79-3) → (Z)-N,N-diethyl-2-(4-(5-(oxiran-2-ylmethoxy)-1,2-diphenylpent-1-en-1-yl)phenoxy)ethan-1-amine

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydroxide / ethyl acetate / 0.5 h 2.1: tert.-butyl lithium / pentane; tetrahydrofuran / 18.5 h / -40 - 20 °C 3.1: tetrabutylammomium bromide; sodium hydroxide 3.2: 15 h / 20 °C View Scheme

clomiphene citrate (7599-79-3) → (Z)-1-(1,4,7,10-tetraazacyclododecan-1-yl)-3-((5-(4-(2-(diethylamino)ethoxy)phenyl)-4,5-diphenylpent-4-en-1-yl)oxy)propan-2-ol

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium hydroxide / ethyl acetate / 0.5 h 2.1: tert.-butyl lithium / pentane; tetrahydrofuran / 18.5 h / -40 - 20 °C 3.1: tetrabutylammomium bromide; sodium hydroxide 3.2: 15 h / 20 °C 4.1: toluene / 16 h / 100 °C View Scheme

clomiphene citrate (7599-79-3) → (Z)-1-(1,4,8,11-tetraazacyclotetradecan-1-yl)-3-((5-(4-(2-(diethylamino)ethoxy)phenyl)-4,5-diphenylpent-4-en-1-yl)oxy)propan-2-ol

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium hydroxide / ethyl acetate / 0.5 h 2.1: tert.-butyl lithium / pentane; tetrahydrofuran / 18.5 h / -40 - 20 °C 3.1: tetrabutylammomium bromide; sodium hydroxide 3.2: 15 h / 20 °C 4.1: toluene / 100 °C View Scheme

clomiphene citrate (7599-79-3) → tri-tert-butyl (Z)-11-(3-((5-(4-(2-(diethylamino)ethoxy)phenyl)-4,5-diphenylpent-4-en-1-yl)oxy)-2-hydroxypropyl)-1,4,8,11-tetraazacyclotetradecane-1,4,8-tricarboxylate

Conditions	Yield
Multi-step reaction with 5 steps 1.1: sodium hydroxide / ethyl acetate / 0.5 h 2.1: tert.-butyl lithium / pentane; tetrahydrofuran / 18.5 h / -40 - 20 °C 3.1: tetrabutylammomium bromide; sodium hydroxide 3.2: 15 h / 20 °C 4.1: toluene / 100 °C 5.1: acetonitrile View Scheme

clomiphene citrate (7599-79-3) → C42H63N5O3*(x)ClH

Conditions	Yield
Multi-step reaction with 6 steps 1.1: sodium hydroxide / ethyl acetate / 0.5 h 2.1: tert.-butyl lithium / pentane; tetrahydrofuran / 18.5 h / -40 - 20 °C 3.1: tetrabutylammomium bromide; sodium hydroxide 3.2: 15 h / 20 °C 4.1: toluene / 100 °C 5.1: acetonitrile 6.1: hydrogenchloride; triethylsilane / water; methanol / 4 h / 20 °C View Scheme

clomiphene citrate (7599-79-3) → C40H59N5O3*(x)ClH

Conditions	Yield
Multi-step reaction with 5 steps 1.1: sodium hydroxide / ethyl acetate / 0.5 h 2.1: tert.-butyl lithium / pentane; tetrahydrofuran / 18.5 h / -40 - 20 °C 3.1: tetrabutylammomium bromide; sodium hydroxide 3.2: 15 h / 20 °C 4.1: toluene / 16 h / 100 °C 5.1: hydrogenchloride / water / pH 5 - 7 View Scheme

clomiphene citrate (7599-79-3) → (Z)-1-<4-(2-diethylaminoethoxy)phenyl>-1,2-diphenyl-1-penten-5-ol (133157-86-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / ethyl acetate / 0.5 h 2: tert.-butyl lithium / pentane; tetrahydrofuran / 18.5 h / -40 - 20 °C View Scheme

Upstream product

• 77-92-9 citric acid 
• 50-41-9 clomifene citrate 
• 19957-52-9 2-{4-(1,2-diphenylethenyl)phenoxy}-N,N-diethylethanamine hydrochloride 
• 911-45-5 clomiphene 
• 911-45-5 clomiphene 
• 73404-00-9 1-{4-[2-(diethylamino)ethoxy]phenyl}-1,2-diphenylethanol 

Downstream Products

• 911-45-5 clomiphene 

Relevant articles and documents

PROCESS FOR THE PREPARATION OF ENCLOMIPHENE CITRATE HAVING NEEDLE SHAPED CRYSTAL HABIT.

The present invention relates an improved and well reproducible process for the preparation of Enclomiphene citrate having needle shaped crystal habit, and moreover, it is also related to a solid form of Enclomiphene citrate.

PROCESS FOR THE PREPARATION OF CLOMIPHENE

An improved process for the preparation of the active pharmaceutical ingredient Clomiphene and, in particular, trans-Clomiphene, using acetic acid or trifluoroacetic acid is disclosed.