53221-14-0

Basic information

• Product Name: 2-(2,7-DICHLORO-9H-FLUORENYL-4-YL)OXIRANE
• Synonyms: 2-(2,7-DICHLORO-9H-FLUORENYL-4-YL)OXIRANE;2-(2,7-Dichloro-9H-fluoren-4-yl)oxirane;5-Oxiranyl-2,7-dichlorofluorene;(2,7-Dichloro-9H-fluoren-4-yl)oxirane;2,( 2, 7-diCHLORO-9H FLUORENE-4-YL)OXIRANE
• CAS NO: 53221-14-0
• Molecular Formula: C₁₅H₁₀Cl₂O
• Molecular Weight: 277.149
• EINECS: 922-480-9
• Product Categories: Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 53221-14-0.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 442.0±45.0 °C(Predicted)
• Appearance: white crystal powder
• Density: 1.449±0.06 g/cm3(Predicted)
• Solubility: Chloroform, Dichloromethane
• CAS DataBase Reference: 2-(2,7-DICHLORO-9H-FLUORENYL-4-YL)OXIRANE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-(2,7-DICHLORO-9H-FLUORENYL-4-YL)OXIRANE(53221-14-0)
• EPA Substance Registry System: 2-(2,7-DICHLORO-9H-FLUORENYL-4-YL)OXIRANE(53221-14-0)

Safety Data

• Hazardous Substances Data: 53221-14-0(Hazardous Substances Data)

Usage

Chemical Properties

Yellow Solid

Synthetic route

2-chloro-1-(2, 7-dichloro-9H-fluoren-4-yl) ethanol → 2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0)

Conditions	Yield
With sodium methylate at 50 - 60℃;
With sodium hydroxide In methanol Reflux;
With sodium ethanolate In ethanol Large scale;	235 kg

2,7-dichloro-9H-fluorene (7012-16-0) → 2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: aluminum (III) chloride / dichloromethane / -5 - 0 °C 2: sodium tetrahydroborate / ethanol / 1 h / -5 - 5 °C 3: sodium methylate / 50 - 60 °C View Scheme
Multi-step reaction with 3 steps 1: aluminum (III) chloride / dichloromethane / 0 - 5 °C 2: sodium tetrahydroborate / methanol / 0 - 20 °C 3: sodium hydroxide / methanol / Reflux View Scheme
Multi-step reaction with 3 steps 1: aluminum (III) chloride / dichloromethane / 8 h / 0 - 5 °C / Large scale 2: sodium tetrahydroborate / ethanol / 3 h / -5 - 5 °C / Large scale 3: sodium ethanolate / ethanol / Large scale View Scheme

2-chloro-1-(2,7-dichloro-9H-fluoren-4-yl)-ethan-1-one → 2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / ethanol / 1 h / -5 - 5 °C 2: sodium methylate / 50 - 60 °C View Scheme
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / methanol / 0 - 20 °C 2: sodium hydroxide / methanol / Reflux View Scheme
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / ethanol / 3 h / -5 - 5 °C / Large scale 2: sodium ethanolate / ethanol / Large scale View Scheme

9H-fluorene (86-73-7) → 2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: chlorine / acetic acid / 15 h / 35 - 45 °C 2: aluminum (III) chloride / dichloromethane / -5 - 0 °C 3: sodium tetrahydroborate / ethanol / 1 h / -5 - 5 °C 4: sodium methylate / 50 - 60 °C View Scheme
Multi-step reaction with 4 steps 1: chlorine; acetic acid / 40 - 42 °C 2: aluminum (III) chloride / dichloromethane / 0 - 5 °C 3: sodium tetrahydroborate / methanol / 0 - 20 °C 4: sodium hydroxide / methanol / Reflux View Scheme
Multi-step reaction with 4 steps 1: hydrogenchloride; chlorine; acetic acid / 10 h / 90 °C / Inert atmosphere; Large scale 2: aluminum (III) chloride / dichloromethane / 8 h / 0 - 5 °C / Large scale 3: sodium tetrahydroborate / ethanol / 3 h / -5 - 5 °C / Large scale 4: sodium ethanolate / ethanol / Large scale View Scheme

chloro-trimethyl-silane (75-77-4) + 2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → (2-chloro-2-(2,7-dichloro-9H-fluoren-4-yl)ethoxy)trimethylsilane

Conditions	Yield
With zinc(II) oxide In dichloromethane at 20℃; for 2h;	73%

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) + dimethyl diselenide (7101-31-7) → 1-(2,7-dichloro-9H-fluoren-4-yl)-2-(methylselanyl)ethan-1-ol

Conditions	Yield
In methanol at 5 - 10℃; Inert atmosphere;	73%

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) + dibutylamine (111-92-2) → 2-dibutylamino-1-(2,7-dichloro-9H-fluoren-4-yl)ethanol (69759-61-1)

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → 2,7-dichloro-4-[2-(dibutyl amino)-1-hydroxyethyl]-9H-fluoren-9-one (53221-25-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: ethanol / 15 h / 78 °C 2: sodium hydroxide; oxygen / ethanol / 6 h / 23 - 70 °C View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → 2-dibutylamino-1-{2,7-dichloro-9-[1-(4-chlorophenyl)meth-(E)-ylidene]-9H-fluoren-4-yl}ethanol + lumefantrine

Conditions	Yield
Multi-step reaction with 2 steps 1: ethanol / 15 h / 78 °C 2: sodium hydroxide / ethanol / 6 h / 23 - 70 °C View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → (RS,Z)-2-dibutylamino-2-[2,7-dichloro-9-(4-chlorobenzylidene)-9H-fluoren-4-yl]ethanol

Conditions	Yield
Multi-step reaction with 4 steps 1: zinc(II) oxide / dichloromethane / 2 h / 20 °C 2: potassium carbonate / acetonitrile / 16 h / Inert atmosphere; Reflux 3: hydrogenchloride / tetrahydrofuran; water / 50 °C / Inert atmosphere 4: sodium hydroxide / ethanol / 1 h / Inert atmosphere; Reflux; Green chemistry View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → N-butyl-N-(1-(2,7-dichloro-9H-fluoren-4-yl)-2-(trimethylsilyloxy)ethyl)butylamine

Conditions	Yield
Multi-step reaction with 2 steps 1: zinc(II) oxide / dichloromethane / 2 h / 20 °C 2: potassium carbonate / acetonitrile / 16 h / Inert atmosphere; Reflux View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → 2-dibutylamino-2-[2,7-dichloro-9H-fluoren-4-yl]ethanol

Conditions	Yield
Multi-step reaction with 3 steps 1: zinc(II) oxide / dichloromethane / 2 h / 20 °C 2: potassium carbonate / acetonitrile / 16 h / Inert atmosphere; Reflux 3: hydrogenchloride / tetrahydrofuran; water / 50 °C / Inert atmosphere View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → 1-(9-benzylidene-2,7-dichloro-9Hfluoren-4-yl)-2-(methylselanyl)ethanol

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 5 - 10 °C / Inert atmosphere 2: sodium hydroxide / methanol / 50 - 70 °C / Inert atmosphere View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → 1-(2,7-dichloro-9-[3,4-dimethoxybenzylidene]-9H-fluoren-4-yl)-2-(methylselanyl)ethanol

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 5 - 10 °C / Inert atmosphere 2: sodium hydroxide / methanol / 50 - 70 °C / Inert atmosphere View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → 5-((2,7-dichloro-4-(1-hydroxy-2-(methylselanyl)ethyl)-9H-fluoren-9-ylidene)methyl)-2-methoxyphenol

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 5 - 10 °C / Inert atmosphere 2: sodium hydroxide / methanol / 50 - 70 °C / Inert atmosphere View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → 1-(2,7-dichloro-9-[3,4-dimethylbenzylidene]-9H-fluoren-4-yl)-2-(methylselanyl)ethanol

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 5 - 10 °C / Inert atmosphere 2: sodium hydroxide / methanol / 50 - 70 °C / Inert atmosphere View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → (2,7-dichloro-9-[2,4,6-trichlorobenzylidene]-9H-fluoren-4-yl)-2-(methylselanyl)ethanol

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 5 - 10 °C / Inert atmosphere 2: sodium hydroxide / methanol / 50 - 70 °C / Inert atmosphere View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → 2-((2,7-dichloro-4-(1-hydroxy-2-(methylselanyl)ethyl)-9H-fluoren-9-ylidene)methyl)phenol

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 5 - 10 °C / Inert atmosphere 2: sodium hydroxide / methanol / 50 - 70 °C / Inert atmosphere View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → 1-(9-[4-bromobenzylidene]-2,7-dichloro-9H-fluoren-4-yl)-2-(methylselanyl)ethanol

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 5 - 10 °C / Inert atmosphere 2: sodium hydroxide / methanol / 50 - 70 °C / Inert atmosphere View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → 1-(2,7-dichloro-9-[2,3-dichlorobenzylidene]-9H-fluoren-4-yl)-2-(methylselanyl)ethanol

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 5 - 10 °C / Inert atmosphere 2: sodium hydroxide / methanol / 50 - 70 °C / Inert atmosphere View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → 1-(2,7-dichloro-9-(4-chlorobenzylidene)-9H-fluoren-4-yl)-2-(methylselanyl)ethanol

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 5 - 10 °C / Inert atmosphere 2: sodium hydroxide / methanol / 50 - 70 °C / Inert atmosphere View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → 1-(9-([1,1'-biphenyl]-4-ylmethylene)-2,7-dichloro-9H-fluoren-4-yl)-2-(methylselanyl)ethanol

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 5 - 10 °C / Inert atmosphere 2: sodium hydroxide / methanol / 50 - 70 °C / Inert atmosphere View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → 4-((2,7-dichloro-4-(1-hydroxy-2-(methylselanyl)ethyl)-9H-fluoren-9-ylidene)methyl)benzene-1,3-diol

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 5 - 10 °C / Inert atmosphere 2: sodium hydroxide / methanol / 50 - 70 °C / Inert atmosphere View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → 1-(2,7-dichloro-9-(4-[dimethylamino]benzylidene)-9Hfluoren-4-yl)-2-(methylselanyl)ethanol

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 5 - 10 °C / Inert atmosphere 2: sodium hydroxide / methanol / 50 - 70 °C / Inert atmosphere View Scheme

2-(2,7-dichloro-9H-fluoren-4-yl)oxirane (53221-14-0) → 1-(2,7-dichloro-9-[2,3,4-trimethoxybenzylidene]-9Hfluoren-4-yl)-2-(methylselanyl)ethanol

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 5 - 10 °C / Inert atmosphere 2: sodium hydroxide / methanol / 50 - 70 °C / Inert atmosphere View Scheme

Upstream product

• 86-73-7 9H-fluorene 
• 7012-16-0 2,7-dichloro-9H-fluorene 

Downstream Products

• 53221-25-3 2,7-dichloro-4-[2-(dibutyl amino)-1-hydroxyethyl]-9H-fluoren-9-one 
• 82186-77-4 2-dibutylamino-1-{2,7-dichloro-9-[1-(4-chlorophenyl)meth-(E)-ylidene]-9H-fluoren-4-yl}ethanol 
• 82186-77-4 lumefantrine 
• 1331642-68-2 (RS,Z)-2-dibutylamino-2-[2,7-dichloro-9-(4-chlorobenzylidene)-9H-fluoren-4-yl]ethanol 
• 69759-61-1 2-dibutylamino-1-(2,7-dichloro-9H-fluoren-4-yl)ethanol 

Relevant articles and documents

An improved manufacturing process for the antimalaria drug coartem. Part II

The manufacturing process for lumefantrine, 2, one of the two active principles in the fixed-dose combination of the anti-malarial drug Coartem, was reworked. For the conversion of 2-chloro-1-(2,7-dichloro-9H-fluoren-4-yl) ethanone, 5, to 2-dibutylamino-1-(2,7-dichloro-9H-fluoren-4-yl)ethanol, 8, a onepot process was developed that eliminated isolation of the epoxide 2-(2,7-dichloro-9H-fluoren-4-yl)oxirane, 7. Significant increase in throughput was achieved by applying new reaction and crystallization conditions for the Knoevenagel condensation of 2-dibutylamino-1-(2,7-dichloro-9H-fluoren-4-yl) ethanol, 8, to 2-dibutylamino-1-{2,7-dichloro-9-[1-(4-chlorophenyl)meth-(Z)- ylidene]-9H-fluoren-4-yl}ethanol, 2.

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