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tilidine

CAS No.
20380-58-9
Chemical Name:
tilidine
Synonyms
tilidine;dl-trans-Tilidine;WDEFBBTXULIOBB-WBVHZDCISA-N;Ethyl (1S,2R)-2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate;rel-2α*-(Dimethylamino)-1-phenyl-3-cyclohexene-1β*-carboxylic acid ethyl ester;rel-2β*-(Dimethylamino)-1β*-phenyl-3-cyclohexene-1α*-carboxylic acid ethyl ester
CBNumber:
CB9895012
Molecular Formula:
C17H23NO2
Molecular Weight:
273.374
MDL Number:
MOL File:
20380-58-9.mol
Last updated:2023-05-04 17:34:35

tilidine Properties

Boiling point bp0.01 95.5-96°
FDA UNII GY33N31E9Y
ATC code N02AX01

SAFETY

Risk and Safety Statements

Symbol(GHS)  GHS hazard pictograms
GHS07
Signal word  Warning
Hazard statements  H302
Precautionary statements  P264-P270-P301+P312-P330-P501

tilidine Chemical Properties,Uses,Production

Originator

Valoron,Goedecke,W. Germany,1970

Uses

Tilidine is an opioid used primarily as a painkiller it inhibits the enzyme adenylyl cyclase.

Definition

ChEBI: Dextilidine is an ethyl 2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate that has S configuration at the carbon bearing the phenyl group and R configuration at the carbon bearing the dimethylamino group. The opioid analgesic tilidine is the racemate comprising equimolar amounts of dextilidine and its enantiomer, ent-dextilidine. A prodrug, tilidine is converted by the liver to the active analgesic, nortilidine; virtually all of the opioid activity resides in the (1S,2R) isomer (i.e. the isomer derived from dextilidine). It has a role as an opioid analgesic and a prodrug. It is an enantiomer of an ent-dextilidine.

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

tilidine Preparation Products And Raw materials

tilidine dl-trans-Tilidine rel-2α*-(Dimethylamino)-1-phenyl-3-cyclohexene-1β*-carboxylic acid ethyl ester rel-2β*-(Dimethylamino)-1β*-phenyl-3-cyclohexene-1α*-carboxylic acid ethyl ester Ethyl (1S,2R)-2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate WDEFBBTXULIOBB-WBVHZDCISA-N 20380-58-9