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TILIDINE HYDROCHLORIDE HEMIHYDRATE

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TILIDINE HYDROCHLORIDE HEMIHYDRATE Basic information

Product Name:
TILIDINE HYDROCHLORIDE HEMIHYDRATE
Synonyms:
  • dl-trans,trans-tildinehydrochloride
  • dl-trans-2-dimethylamino-1-phenyl-cyclohex-3-ene-trans-carbonicacidethyles
  • dl-trans-2-dimethylamino-1-phenyl-cyclohex-3-en-trans-1-carbonsaeureaethyles
  • ethyldl-trans-2-dimethylamino-1-phenyl-3-cyclohexene-1-carboxylate
  • w5759a
  • ethyl trans-(±)-2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate hydrochloride
  • TilidinHCl,Hemihydrate
  • Tilidinhydrochloride,Hemihydrate
CAS:
27107-79-5
MF:
C17H26ClNO3
MW:
327.85
EINECS:
248-226-0
Product Categories:
  • Amines
  • Chiral Reagents
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
Mol File:
27107-79-5.mol
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TILIDINE HYDROCHLORIDE HEMIHYDRATE Chemical Properties

Melting point:
149-152?C
Flash point:
9℃
storage temp. 
-20°C Freezer
solubility 
Freely soluble in water, very soluble in methylene chloride, freely soluble in ethanol (96 per cent).
form 
Solid
color 
White to Off-White
Stability:
Hygroscopic
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Safety Information

Hazard Codes 
F,T
Risk Statements 
11-23/24/25-39/23/24/25
Safety Statements 
7-16-36/37-45
RIDADR 
UN1230 - class 3 - PG 2 - Methanol, solution
WGK Germany 
1
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TILIDINE HYDROCHLORIDE HEMIHYDRATE Usage And Synthesis

Chemical Properties

TILIDINE HYDROCHLORIDE HEMIHYDRATE is White Solid

Originator

Valoron,Goedecke,W. Germany,1970

Uses

TILIDINE HYDROCHLORIDE HEMIHYDRATE is a controlled substance (opiate). Analgesic. It is used in clinical trial in comparison with Nefopam. Tilidine is one of the most widely used narcotics in Germany and Belgium.

Manufacturing Process

In a first step, dimethylamine is reacted with crotonaldehyde to give 1- (dimethylamino)-1,3-butadiene.
A solution of 194 grams (2 mols) of fresh-distilled 1-(dimethylamino)-1,3- butadiene is combined at room temperature in a 1 liter round-bottom flask with 352 grams (2 mols) atropic acid ethyl ester. After being stirred for about 10 minutes, the reaction mixture gradually becomes exothermic. By cooling with ice water, the contents of the flask are kept at a temperature of 40° to 60°C. After the reaction has ceased, the mixture is kept overnight (about 8 to 24 hours) at room temperature. The next day the viscous product is dissolved in 10 liters of ether and precipitated with ethereal hydrogen chloride forming the corresponding hydrochloride. By fractional crystallization from ethyl acetate/methyl ethyl ketone (10:1), an almost complete separation of the isomeric cis/trans isomers (I) and (II) is achieved. The separation can be carried out very easily due to the low solubility of the 1 1/2-hydrate of (I). Therefore, during the crystallization a sufficient quantity of water for the formation of the 1 1/2-hydrate of (I) is added to the mixture of solvents, whereby (I) readily precipitates.
Isomer (I): 4-phenyl-3-cis-dimethylamino-4-cis-carbethoxy-?1- cyclohexenehydrochloride, [ethyl-cis-3-(dimethylamino)-4-phenyl-1- cyclohexene-4-carboxylate hydrochloride] , MP 84°C (the free base boils at 97.5° to 98°C at 0.01 mm pressure), 64.4% yield.
Isomer (II): 4-phenyl-3-trans-dimethylamino-4-trans-carbethoxy-?1- cyclohexenehydrochloride, [ethyl-trans-3-(dimethylamino)-4-phenyl-1- cyclohexene-4-carboxylate hydrochloride], MP 159°C (the free base boils at 95.5° to 96°C at 0.01 mm pressure), 22.2% yield.

Therapeutic Function

Analgesic

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