WARNING: Fentanyl is extremely dangerous. Do NOT ATTEMPT this synthesis without naloxone present!
DISCLAIMER: This method does not produce high purify fentanyl (avg. is 13.6%, range 0.2% to 36.4%)
The original paper talking about this procedure can be found here.
Fentanyl is a very powerful opioid, much more powerful than both morphine and heroin.
The procedure listed below is a one-pot synthesis. It is attractive to the clandestine chemist due to it's possibility to be done in 3 steps all at room temperature. The only caveat is the requirement of N₂ gas.
The reaction scheme is shown below:
To a stirred suspension of 4-piperidone hydrochloride (15.36 g, 0.1 mol) in dichloroethane (450 ml), triethylamine (27.87 ml, 0.2 mol) and phenylacetaldehyde (11.17 ml, 0.1 mol) were added and stirred for half an hour at room temperature under N2. Thereafter sodium triacetoxyborohydride (30 g, 0.14 mol) was added to the reaction mixture with continuous stirring. Reaction mixture was further stirred for 24 h. Aniline (9.12 ml, 0.1 mol), acetic acid (11.53 ml, 0.2 mol) and sodium triacetoxyborohydride (30 g, 0.14 mol) were then added and again stirred for 24 h. Propionyl chloride (26.16 ml, 0.3 mol) was then added dropwise and the mixture was stirred for 2 h. The reaction mixture was then diluted with dichloromethane and washed with 4% aqueous sodium hydroxide solution followed by water. The organic phase was then shaken with 2N HCl. The organic layer was separated and the aqueous layer was extracted with DCM. Combined organic phase was dried over sodium sulfate and concentrated to give crude HCl salt of fentanyl. Crude product was recrystallised with acetone to give white powder of fentanyl hydrochloride. The salt was treated with 20% NaOH to give fentanyl which was recrystallised from petroleum ether (60–80°)
Yield: 13.44 g (40 %)
m.p. 82–83 °C.
Literature
The paper on synthesis of fentanyl in this manner can be found here.
DISCLAIMER: This method does not produce high purify fentanyl (avg. is 13.6%, range 0.2% to 36.4%)
The original paper talking about this procedure can be found here.
Fentanyl is a very powerful opioid, much more powerful than both morphine and heroin.
The procedure listed below is a one-pot synthesis. It is attractive to the clandestine chemist due to it's possibility to be done in 3 steps all at room temperature. The only caveat is the requirement of N₂ gas.
The reaction scheme is shown below:
To a stirred suspension of 4-piperidone hydrochloride (15.36 g, 0.1 mol) in dichloroethane (450 ml), triethylamine (27.87 ml, 0.2 mol) and phenylacetaldehyde (11.17 ml, 0.1 mol) were added and stirred for half an hour at room temperature under N2. Thereafter sodium triacetoxyborohydride (30 g, 0.14 mol) was added to the reaction mixture with continuous stirring. Reaction mixture was further stirred for 24 h. Aniline (9.12 ml, 0.1 mol), acetic acid (11.53 ml, 0.2 mol) and sodium triacetoxyborohydride (30 g, 0.14 mol) were then added and again stirred for 24 h. Propionyl chloride (26.16 ml, 0.3 mol) was then added dropwise and the mixture was stirred for 2 h. The reaction mixture was then diluted with dichloromethane and washed with 4% aqueous sodium hydroxide solution followed by water. The organic phase was then shaken with 2N HCl. The organic layer was separated and the aqueous layer was extracted with DCM. Combined organic phase was dried over sodium sulfate and concentrated to give crude HCl salt of fentanyl. Crude product was recrystallised with acetone to give white powder of fentanyl hydrochloride. The salt was treated with 20% NaOH to give fentanyl which was recrystallised from petroleum ether (60–80°)
Yield: 13.44 g (40 %)
m.p. 82–83 °C.
Literature
The paper on synthesis of fentanyl in this manner can be found here.
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