2709-56-0

Basic information

• Product Name: Flupentiol
• Synonyms: CIS(Z)-FLUPENTIXOL 2HCL;(alpha,beta)-flupenthixol;1-piperazineethanol,4-(3-(2-(trifluoromethyl)-9h-thioxanthen-9-ylidene)propy;2-trifluoromethyl-9-(3-(4-(beta-hydroxyethyl)-1-piperazinyl)propylidene)thio;4-(3-(2-(trifluoromethyl)-9h-thioxanthen-9-ylidene)propyl)-1-piperazineethan;4-(3-(2-(trifluoromethyl)thioxanthen-9-ylidene)propyl)-1-piperazineethano;4-(3-(2-(trifluoromethyl)thioxanthen-9-ylidene)propyl)-1-piperazineethanol;emergil
• CAS NO: 2709-56-0
• Molecular Formula: C₂₃H₂₅F₃N₂OS
• Molecular Weight: 434.52
• EINECS: 220-304-9
• Mol File: 2709-56-0.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 554.7±50.0 °C(Predicted)
• Appearance: white or off-white/solid
• Density: 1.2118 (estimate)
• Refractive Index: 1.607
• Solubility: H2O: soluble
• PKA: pKa 7.80 (Uncertain)
• CAS DataBase Reference: Flupentiol(CAS DataBase Reference)
• NIST Chemistry Reference: Flupentiol(2709-56-0)
• EPA Substance Registry System: Flupentiol(2709-56-0)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22
• Safety Statements: 36/37/39
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• RTECS: TL9900000
• Hazardous Substances Data: 2709-56-0(Hazardous Substances Data)

Usage

Definition

ChEBI: A thioxanthene derivative having a trifluoromethyl substituent at the 2-position and a 3-(4-(2-hydroxyethyl)piperazin-1-yl)propylidene group at the 10-position with undefined double bond stereochemistry.

Therapeutic Function

Tranquilizer

InChI:InChI=1/C23H27F3N2OS/c24-23(25,26)17-7-8-22-20(16-17)18(19-4-1-2-6-21(19)30-22)5-3-9-27-10-12-28(13-11-27)14-15-29/h1-2,4-8,16,20,22,29H,3,9-15H2

Synthetic route

(Z)-flupentixol p-chlorobenzoate dihydrochloride → cis-(Z)-flupenthixol (2709-56-0)

Conditions	Yield
Stage #1: (Z)-flupentixol p-chlorobenzoate dihydrochloride With potassium hydroxide In methanol; water at 55℃; for 1h; Stage #2: In water; toluene at 70℃; Stage #3: With cyclohexane at 60℃;	70%

1-(2-hydroxyethyl)piperazine (103-76-4) + 2-trifluoromethyl-9-(2-propenylidene)thioxanthene (28973-34-4) → cis-(Z)-flupenthixol (2709-56-0) + flupenthixol (53772-85-3)

Conditions	Yield
Stage #1: 1-(2-hydroxyethyl)piperazine; 2-trifluoromethyl-9-(2-propenylidene)thioxanthene at 100℃; under 0.2 - 1 Torr; for 7h; Stage #2: In water; toluene at 70℃; for 0.25h; Stage #3: With sulfuric acid; ammonia more than 3 stages;

n-decanoyl chloride (112-13-0) + cis-(Z)-flupenthixol (2709-56-0) → (Z)-flupentixol decanoate dihydrochloride

Conditions	Yield
Stage #1: n-decanoyl chloride; cis-(Z)-flupenthixol In acetone for 1.5h; Heating / reflux; Stage #2: With hydrogenchloride In ethyl acetate at 5 - 25℃;	85%

4-chloro-benzoyl chloride (122-01-0) + cis-(Z)-flupenthixol (2709-56-0) + flupenthixol (53772-85-3) → (Z)-flupentixol p-chlorobenzoate dihydrochloride + (E)-flupentixol p-chlorobenzoate hydrochloride

Conditions	Yield
Stage #1: 4-chloro-benzoyl chloride; cis-(Z)-flupenthixol; flupenthixol In ethyl acetate at 40 - 70℃; for 1h; Stage #2: With hydrogenchloride In water at 40℃; for 0.25h;	A 33% B n/a

Upstream product

• 103-76-4 1-(2-hydroxyethyl)piperazine 
• 28973-34-4 2-trifluoromethyl-9-(2-propenylidene)thioxanthene 
• 850808-70-7 2-trifluoromethyl-9-allyl-9-thioxanthenol 
• 53772-85-3 flupenthixol 
• 95365-88-1 cis-10-(3-Dimethylamino-propyliden)-2-trifluormethyl-thiaxanthen 
• 2340-57-0 (9RS)-9-[3-dimethylamino-propyl]-2-(trifluoromethyl)-9H-thioxanthene-9-ol 

Downstream Products

• 2413-38-9 flupentixol dihydrochloride 
• 2413-38-9 flupentixol hydrochloride 
• 90331-36-5 Flupentixol-4-methyliodid 
• 90331-35-4 Flupentixol-1-methyliodid 

Relevant articles and documents

A hydrochloric acid flupentixol preparation method

The invention provides a preparation method of flupentixol dihydrochloride, which comprises the following steps: reacting and dehydrating 10-hydroxy-10-(3-dimethylaminopropyl)-2-trifluoromethyl thioxanthene and sulfoxide chloride or acetic anhydride to prepare high-content Z-type 10-[3-(EZ)-dimethylaminopropyl]-2-trifluoromethyl thioxanthene, reacting with N-hydroxyethyl piperazidine to prepare flupentixol base, and finally, introducing sufficient hydrochloric acid gas into the flupentixol base to prepare the high-content Z-type flupentixol dihydrochloride. The method has the advantages of fewer steps, high yield and high product purity, is simple to operate, and does not use any extremely toxic substance to pollute the environment. The Z-type flupentixol dihydrochloride content in the flupentixol dihydrochloride prepared by the method is 42-52%, and conforms to the quality standard specification for flupentixol dihydrochloride in European Pharmacopoeia.

PROCESS FOR THE PREPARATION OF Z-FLUPENTIXOL

The present invention relates to a process for the separation of flupentixol isomers, particularly, a process for the preparation of Z-flupentixol and the decanoate ester and novel synthetic intermediates thereof.