1480-19-9

Basic information

• Product Name: Fluanisone
• Synonyms: Fluanisone;1-Butanone, 1-(4-fluorophenyl)-4-4-(2-methoxyphenyl)-1-piperazinyl-;2028 Md;4-[4-(o-Methoxyphenyl)-1-piperazinyl]-p-fluorobutyrophenone;4'-Fluoro-4-[4-(o-methoxyphenyl)-1-piperazinyl]butyrophenone;Anti-pica;Butyrophenone, 4'-fluoro-4-[4-(o-methoxyphenyl)-1-piperazinyl]-;Fluanison
• CAS NO: 1480-19-9
• Molecular Formula: C₂₁H₂₅FN₂O₂
• Molecular Weight: 356.439
• EINECS: 216-038-8
• Product Categories: Aromatics;Heterocycles;Intermediates & Fine Chemicals;Neurochemicals;Pharmaceuticals
• Mol File: 1480-19-9.mol
• Article Data: 4

Chemical Properties

• Melting Point: 67.5-68.5°
• Boiling Point: 511.8°Cat760mmHg
• Flash Point: 263.3°C
• Appearance: /
• Density: 1.146
• Vapor Pressure: 1.38E-10mmHg at 25°C
• Refractive Index: 1.557
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 7.43±0.10(Predicted)
• CAS DataBase Reference: Fluanisone(CAS DataBase Reference)
• NIST Chemistry Reference: Fluanisone(1480-19-9)
• EPA Substance Registry System: Fluanisone(1480-19-9)

Safety Data

• Hazardous Substances Data: 1480-19-9(Hazardous Substances Data)

Usage

Originator

Sedalande ,J and J

Uses

Different sources of media describe the Uses of 1480-19-9 differently. You can refer to the following data:
1. Fluanisone is a butyrophenone derivative with sedative properties. It is a typical antipsychotic and is used in the treatment of schizophrenia.
2. Fluanisone is a neuroleptic with sedative properties and relatively poorly expressed antipsychotic action. It is used as an independent or adjuvant drug for psychomotor excitement in severe and chronic schizophrenia and for manic-depressive disorder.

Manufacturing Process

To a suspension of 341 parts of aluminum chloride in 1740 parts of carbon disulfide are added 96 parts of fluorobenzene with stirring and cooling. While the temperature is maintained at about 10°C, 141 parts of γ-chlorobutyryl chloride are added. After the addition is completed, the cooling bath is removed and the stirring is continued for 2 hours. The reaction mixture is poured into ice water. The organic layer is separated, washed with water, dried over anhydrous sodium sulfate, and filtered. The filtrate is concentrated under reduced pressure, and the residue is distilled to yield γ-chloro-p-fluorobutyrophenone boiling at about 136°-142°C/6 mmA mixture of 6.6 parts of γ-chloro-p-fluoro-butyrophenone and 12.5 parts of 1- (o-anisyl)piperazine is heated for 10 hours at a temperature of 110°C. The reaction mixture is treated with 800 parts of ether and filtered. The ether layer is washed with water, dried over anhydrous potassium carbonate and filtered, whereupon hydrogen chloride gas is introduced into the solution. The precipitate is collected on a filter and dissolved in a mixture of 240 parts of 2- propanol and 80 parts of acetone to yield 1-[γ-(p-fluorobenzoyl)propyl]-4-(o-anisyl)piperazine hydrochloride. This monohydrochloride is collected on a filter and dissolved in 240 parts of 2-propanol. Anhydrous, gaseous hydrogen chloride is passed through the solution. On cooling, the 1-[γ-(p-fluorobenzoyl) propyl]-4-(o-anisyl)piperazine dihydrochloride precipitates.A second crop of product is obtained by passing hydrogen chloride gas through the solution of mother liquors. The pale-brown, amorphous powder is collected on a filter and found to melt at about 205°-205.5°C.This salt is dissolved in water and treated with sodium hydroxide. The precipitated base is recovered by filtration and recrystallized from diisopropyl ether. The white crystals melt at about 67.5°-68.5°C.

Therapeutic Function

Neuroleptic

Synthesis

Fluanisone, 4′-fluoro-4-[4-(o-methoxyphenyl)-1-piperazinyl]-butyrophenone (6.3.12), is synthesized by reacting 1-(2′-methoxyphenyl)-piperazine with 4
-chloro- 4′-fluorobutyrophenone (6.3.4) [50].

InChI:InChI=1/C21H25FN2O2/c1-26-21-7-3-2-5-19(21)24-15-13-23(14-16-24)12-4-6-20(25)17-8-10-18(22)11-9-17/h2-3,5,7-11H,4,6,12-16H2,1H3

Synthetic route

Anisopirol (857-62-5) → fluanisone (1480-19-9)

Conditions	Yield
With sodium hydrogencarbonate; Dess-Martin periodane In dichloromethane at 20℃; for 3h; Inert atmosphere;	92%

4-fluorobenzaldehyde (459-57-4) → fluanisone (1480-19-9)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: zinc / tetrahydrofuran / 0.17 - 0.25 h / 20 °C 1.2: 3 h / 0 °C 2.1: potassium carbonate; tetra-(n-butyl)ammonium iodide / acetonitrile / 5 h / Reflux 3.1: dimethylsulfide borane complex / tetrahydrofuran / 1.5 h / 0 - 20 °C 3.2: 1 h / 0 °C 4.1: pyridinium chlorochromate / dichloromethane / 2 h / 20 °C 5.1: acetic acid / methanol / 1 h / 0 - 20 °C 5.2: 3 h / 0 - 20 °C 6.1: 10% Pd/C; hydrogen / methanol / 10 h / 20 °C 7.1: Dess-Martin periodane; sodium hydrogencarbonate / dichloromethane / 3 h / 20 °C / Inert atmosphere View Scheme

1-(4-fluorophenyl)-3-buten-1-ol (86718-78-7, 136185-86-9) → fluanisone (1480-19-9)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: potassium carbonate; tetra-(n-butyl)ammonium iodide / acetonitrile / 5 h / Reflux 2.1: dimethylsulfide borane complex / tetrahydrofuran / 1.5 h / 0 - 20 °C 2.2: 1 h / 0 °C 3.1: pyridinium chlorochromate / dichloromethane / 2 h / 20 °C 4.1: acetic acid / methanol / 1 h / 0 - 20 °C 4.2: 3 h / 0 - 20 °C 5.1: 10% Pd/C; hydrogen / methanol / 10 h / 20 °C 6.1: Dess-Martin periodane; sodium hydrogencarbonate / dichloromethane / 3 h / 20 °C / Inert atmosphere View Scheme

1-[1-(benzyloxy)-but-3-enyl]-4-fluorobenzene (1143515-07-4) → fluanisone (1480-19-9)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: dimethylsulfide borane complex / tetrahydrofuran / 1.5 h / 0 - 20 °C 1.2: 1 h / 0 °C 2.1: pyridinium chlorochromate / dichloromethane / 2 h / 20 °C 3.1: acetic acid / methanol / 1 h / 0 - 20 °C 3.2: 3 h / 0 - 20 °C 4.1: 10% Pd/C; hydrogen / methanol / 10 h / 20 °C 5.1: Dess-Martin periodane; sodium hydrogencarbonate / dichloromethane / 3 h / 20 °C / Inert atmosphere View Scheme

4-(benzyloxy)-4-(4-fluorophenyl)-butan-1-ol (1402042-55-0) → fluanisone (1480-19-9)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: pyridinium chlorochromate / dichloromethane / 2 h / 20 °C 2.1: acetic acid / methanol / 1 h / 0 - 20 °C 2.2: 3 h / 0 - 20 °C 3.1: 10% Pd/C; hydrogen / methanol / 10 h / 20 °C 4.1: Dess-Martin periodane; sodium hydrogencarbonate / dichloromethane / 3 h / 20 °C / Inert atmosphere View Scheme

4-(benzyloxy)-4-(4-fluorophenyl)-butanal (1402042-56-1) → fluanisone (1480-19-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: acetic acid / methanol / 1 h / 0 - 20 °C 1.2: 3 h / 0 - 20 °C 2.1: 10% Pd/C; hydrogen / methanol / 10 h / 20 °C 3.1: Dess-Martin periodane; sodium hydrogencarbonate / dichloromethane / 3 h / 20 °C / Inert atmosphere View Scheme

Upstream product

• 857-62-5 Anisopirol 
• 1402042-56-1 4-(benzyloxy)-4-(4-fluorophenyl)-butanal 
• 1402042-55-0 4-(benzyloxy)-4-(4-fluorophenyl)-butan-1-ol 
• 1143515-07-4 1-[1-(benzyloxy)-but-3-enyl]-4-fluorobenzene 
• 86718-78-7 1-(4-fluorophenyl)-3-buten-1-ol 
• 459-57-4 4-fluorobenzaldehyde 

Relevant articles and documents

CNS-agent precursor: A simple and efficient synthesis of an antipsychotic drug fluanisone

An efficient synthesis of antipsychotic drug fluanisone has been carried out in seven steps with an overall yield of 32.2%. The synthesis was started from 4-fluorobenzaldehyde. All the reactions were very clean and the isolation of products was very easy.

Process for the production of dry pharmaceutical forms and the thus obtained pharmaceutical compositions

A process for the production of a solid dispersion of at least one therapeutic agent in a hydrophilic carrier having enhanced solubility in an aqueous media comprising dissolving at least one therapeutic agent in a volatile organic solvent containing a very hydrophilic polymer and evaporating the solvent to dryness to form a co-precipitate of therapeutic agent and hydrophilic polymer and the resulting products and their therapeutic method of use.