A new path of synthesis of 1,2,5-trimethyl-4-piperidone ketone from methylisopropenyl ketone (II) under the schema:
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A new convenient procedure was developed to synthesize 1,2,5-trimethyl-4-piperidone. Methylisopropenyl ketone reacts with Me3SiCl in the presence of triethylamine of Et3N and NaI to form 2-trimethylsilyloxy-3-methyl-1,3-butadiene that further reacts with acetaldehyde acetals to yield 5-alkoxy-2-methyl-1-hexene-3-ones. The subsequent treatment of CH3NH2 provides 1,2,5-trimethyl-4-piperidone having a total yield of 40-44 % at three stages.
Experimental part
2-trimethylsilyloxy-3-methyl-1,3-butadiene (III)
To an intermixture of 16 g (0,12 moles) methylisopropenyl ketone (II), 80 mls MeCN and 16,3 g (0,16 moles) Et3N at intensive stirring add 24,3 g (0,16 moles) inciderated NaI, and then add dropwise 17,5g (0,16 moles) Me3SiCl. Reactionary mass during 15 minute agitate at t=25°Ñ, then 1 h at t=70°Ñ, then chill and add 120 mls of saturated solution NaHCO3. A precipitate filter off, organic bed carefully extract by pentane, wash by water and dry MgSO4. After distillation obtain 15,3 g (82,3 %) III with boiling point 42 Ñ (20 mm )
5-metoxy-2-methyl-1-hexene-3-ones (IV, R=Me)
To an intermixture of 90 g (1 mol) dimethylacetal acetaldehyde and 295 mls 15 % of a solution ZnCl2 in waterless ethyl acetate during 40 mines add dropwise 100,3 g (0,66 moles) III. Self-heating an intermixture up to 35°Ñ is watched. Reactionary mass agitate within 1 h at 40°Ñ, then chill up to 20°Ñ and add by saturated solution NaHCOs (500 mls). Organic bed separate, aqueous carefully extract by an ether. Integrated organic bed and the ethereous extracts dry Ka2CO3. After distillation of resultant of reaction would obtain 62 g (68,2 %) 5-metoxy-2-methyl-1-hexene-3-ones IV (R=Me) with boiling point 77°C (10 mm).
5-etoxy-2-methyl-1-hexene-3-ones (IV, R=Et)
Is received from diethylacetal acetaldehyde on a similar procedure with a yield 60,6 %, with boiling point 84°Ñ (10 mm )
1,2,5-trimethyl-4-piperidone (I).
An intermixture of 3,4 g (0,024 moles) IV (R=Me). 5 mls 20 % of water solution MeNH2 (0,032 moles) and 3,5 mls MeOH(methanol) heat up in the soldered glass ampula at 60°Ñ within 4 hours. Then an intermixture chill, acidify 18 % HÑl up to an acid reaction, ÌåÎÍ distil off in small empty space and reactionary mass extract by an ether for removal of neutral yields. Then an intermixture handle at refrigerating by solid alkali and carefully extract by an ether. An ethereous extract dry MgS04. After distillation obtain 2,4 g (71,2 %) I with boiling point 82°C (10 mm ) C8H15NO
On a similar procedure piperidoneI is obtained from IV (R == Et) with a yield 45,5 %.
This method I translate from Russian.
I have no place to put the schema of synthesis, if are you necessary see that, write to me.
My thoughts:
Trimetilchlorinesilicone Me3SiCl sells in chemical shops without restrictions.
Methylisopropenyl ketone (II) it is possible easily to receive from methylethyl ketone and powder paraform CH2O at the presence of alkali.
If to use acetone, powder paraform CH2O and alkali, and then under the schema, we shall receive unreplaced in 2 standing piperidon.
The acetals obtain from spirit and aldehyde at the presence of waterless acids.
If to use in second stages formaldehyde dimethyl acetal we shall receive unreplaced in 3 standing piperidon.
In the third stage it is possible to use any secondary amine - path to any other derivant of fentanyl.
Use higher-boiling amine, for example phenethylamin, it is possible to do without ampulas.
Thus, it is simple synthesis from accessible and not checked builders, OTC any (!) derivant of fentanyl !
Translation about biological property 2,5 dimethylfentanyl I shall write little bit later.
Fallen_Angel
