* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Octyl amine hydrochloride were added to 1,200 ml of dimethylformamide (DMF), and the mixture was vigorously stirred while gradually heating the internal temperature to 160 ° C under nitrogen substitution. The reaction temperature is gradually heated for 2 to 3 hours and then maintained at the same temperature for 7 hours.After completion of the thin layer chromatographic phase reaction, the reaction mixture is cooled to 0 ° C and the reaction mixture is filtered using a filter paper to obtain the first reaction product. In the above reaction, the filtered filtrate is distilled off under reduced pressure, then cooled, diluted with acetonitrile to obtain crystals, filtered on a filter paper, and pulverized to obtain a second crystal.The first and second reactants are combined and dissolved in methanol. The dissolved solution is decolorized with carbon, filtered, and the filtrate is distilled under reduced pressure. The reduced pressure distilled reaction is cooled, recrystallized with acetonitrile, cooled and filtered to give decolorized white crystals.The crystals were dried under reduced pressure at 60 DEG C for 72 hours to obtain 196.0 g (yield: 94.2percent, MP 215-217 DEG C) of octeneidine hydrochloride in a granular state.
Reference:
[1] Patent: KR2017/13425, 2017, A, . Location in patent: Paragraph 0088; 0089
2
[ 2162-98-3 ]
[ 64690-19-3 ]
[ 70775-75-6 ]
Yield
Reaction Conditions
Operation in experiment
39%
at 120 - 180℃;
6.18 g of 4-octylaminopyridine base and 3.15 g of 1,10-dichlorodecane were mixed, slowly heated to 120 ° C., exothermically reacted to 180 ° C., and thin layer chromatography (TLC) to confirm the reaction. 25 ml of dimethyformamide (DMF) was added and the mixture was warmed and completely dissolved again. The mixture was cooled to 0 ° C to precipitate crystals, which were filtered and dried under reduced pressure at 60 ° C. Through the above process, 7.3 g of 1,10-bisoctylaminopyridinium decane hydrochloride (Yield: 39.0percent, mp 215 to 217 ° C) was obtained
6.18 g of 4-octylaminopyridine base and 3.15 g of <strong>[2162-98-3]1,10-dichlorodecane</strong> were mixed, slowly heated to 120 C., exothermically reacted to 180 C., and thin layer chromatography (TLC) to confirm the reaction. 25 ml of dimethyformamide (DMF) was added and the mixture was warmed and completely dissolved again. The mixture was cooled to 0 C to precipitate crystals, which were filtered and dried under reduced pressure at 60 C. Through the above process, 7.3 g of 1,10-bisoctylaminopyridinium decane hydrochloride (Yield: 39.0%, mp 215 to 217 C) was obtained
In water;
Example 1 20.6 g (0.1 mol) of 4-octylaminopyridine, 10.5 g (0.05 mol) of <strong>[2162-98-3]1,10-dichlorodecane</strong> and 30 ml of demineralized water were combined and refluxed with stirring. The initially cloudy, yellowish solution became clear and yellow after 3 hours. After the mass had been stirred for a further hour at reflux, it was cooled to 5 C. The resulting white, semisolid paste was filtered off with suction, and the product octenidine dihydrochloride in the form of colourless crystals was washed with iced water.
Example 8 20.6 g (0.1 mol) of 4-octylaminopyridine, 10.5 g (0.05 mol) of <strong>[2162-98-3]1,10-dichlorodecane</strong> and 30 ml of white spirit (boiling point 155 to 200 C.) were combined and heated to 130 C. The exothermic reaction causes the temperature to increase to 155 C., and at the same time white crystal precipitate out. The reaction mixture was stirred for a further 4 hours at 140 C., and after cooling to room temperature the very fine crystal sludge was filtered over a filterpaper and washed with petroleum ether, giving a beige, solid mass. The reaction product octenidine dihydrochloride in this example is very difficult to filter off with suction since it is produced in very fine form.
1,10-bis-(4-chloropyridin-1 (4H)-yl)decane[ No CAS ]
[ 142-95-0 ]
[ 70775-75-6 ]
Yield
Reaction Conditions
Operation in experiment
94.2%
In N,N-dimethyl-formamide at 160℃; Inert atmosphere;
2-2 Second octylation substitution reaction
Octyl amine hydrochloride were added to 1,200 ml of dimethylformamide (DMF), and the mixture was vigorously stirred while gradually heating the internal temperature to 160 ° C under nitrogen substitution. The reaction temperature is gradually heated for 2 to 3 hours and then maintained at the same temperature for 7 hours.After completion of the thin layer chromatographic phase reaction, the reaction mixture is cooled to 0 ° C and the reaction mixture is filtered using a filter paper to obtain the first reaction product. In the above reaction, the filtered filtrate is distilled off under reduced pressure, then cooled, diluted with acetonitrile to obtain crystals, filtered on a filter paper, and pulverized to obtain a second crystal.The first and second reactants are combined and dissolved in methanol. The dissolved solution is decolorized with carbon, filtered, and the filtrate is distilled under reduced pressure. The reduced pressure distilled reaction is cooled, recrystallized with acetonitrile, cooled and filtered to give decolorized white crystals.The crystals were dried under reduced pressure at 60 DEG C for 72 hours to obtain 196.0 g (yield: 94.2%, MP 215-217 DEG C) of octeneidine hydrochloride in a granular state.
With sodium hydroxide In water; toluene at 20 - 30℃;
6 EXAMPLE 6: Preparation of octenidine base
30 g of octenidine dihydrochloride obtained in example 4, 300 ml of toluene, 240 ml of 2N aqueous NaOH and 540 ml of deionized water were stirred for 1 hour at 20-25°C. The suspension was filtered obtaining a solid. The biphasic mother liquors were allowed to settle, and the aqueous phase was separated. The aqueous phase and the solid were combined together with 200 ml of toluene, 50 ml of 2N aqueous NaOH and 2 ml of 50% aqueous NaOH and the suspension was stirred at 30°C. The solution obtained was allowed to settle and a tri-phasic mixture was obtained. The upper organic phase was separated, washed with 100 ml of 1 N aqueous NaOH at 20-25°C and the mixture was allowed to settle. A tri-phasic mixture was obtained. The upper organic phase was separated, washed again with 100 ml of 1 N aqueous NaOH at 20-25°C and the mixture was allowed to settle. A tri-phasic mixture was obtained. The upper organic phase was separated, washed again with 100 ml of 1 N aqueous NaOH at 30°C and the mixture was allowed to settle. A bi-phasic mixture was obtained, and the aqueous phase was discarded. The solvent from the organic phase was removed by distillation at reduced pressure at 50°C. The crude thus obtained was triturated with 60 ml of toluene at 50°C for 45 minutes, the suspension was stirred at 20-25°C for about 1 hour and then it was filtered, washing the cake with 5 ml of ethyl acetate. 14.5 g of octenidine base were obtained after drying the solid. Chloride content: 0.05%. Purity (% area, HPLC): 99.9%. XRPD: Diffraction peaks at (2Q, degrees): 5.8, 8.0, 1 1.6, 15.1 , 16.1 , 20.1 , 20.8, 23.4, (0081) 23.8 and 24.3 ± 0.2 (See Figure 4).
84.07 %
With potassium carbonate In water; toluene at 97℃;
1; 4
Dissolve potassium carbonate in water to obtain with a molar concentration of 2 mol/L K2CO3aqueous solution; 2g octenidine dichloride, 20mL toluene and 200mL K2CO3Mix the aqueous solution at 97°C for deprotonation reaction for 10 hours, then use a separatory funnel to separate the water phase and the organic phase of the system after the deprotonation reaction, collect the organic phase, mix 4 g of anhydrous sodium sulfate with the organic phase for dehydration, and filter to remove sodium sulfate; Rotate the filtrate obtained by filtration at 40°C to obtain the crude octenidine base; mix the crude octenidine base with 6 mL of ethyl acetate and petroleum ether prepared from ethyl acetate and petroleum ether at a volume ratio of 20:1 The solution is mixed for recrystallization, and the solid obtained by the recrystallization is pumped dry to obtain octenidine base.
Multi-step reaction with 2 steps
1: hydrogen; 10% Pd/C / ethanol / 80 °C / 2625.26 Torr
2: acetic acid butyl ester / 12 h / Reflux
Multi-step reaction with 2 steps
1.1: sodium tris(acetoxy)borohydride; ethanol / 30 h / 85 °C
2.1: acetic acid butyl ester / 13 h / 95 °C
2.2: 2 h / 90 °C
Multi-step reaction with 2 steps
1: hydrogen; 10% Pd/C / ethanol / 80 °C / 2625.26 Torr
2: acetic acid butyl ester / 12 h / Reflux
Multi-step reaction with 2 steps
1.1: sodium tris(acetoxy)borohydride; ethanol / 30 h / 85 °C
2.1: acetic acid butyl ester / 13 h / 95 °C
2.2: 2 h / 90 °C