109-07-9, 2-Methylpiperazine is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated
Example 16 A 1-liter four-neck flask with a thermometer, stirrer and condenser was charged with 100.0 g of water and 90.0 g (= 0.600 mole) of D-tartaric acid, and after a homogeneous solution was formed, 200.4 g of an aqueous solution containing 50 wt% of racemic 2-methylpiperazine (pure 2-methylpiperazine content = 1.00 mole) and 36.0 g (= 0.600 mole) of acetic acid were added at room temperature. A homogeneous solution was formed at 70 to 75C, and seed crystals were added at 65C, being followed by aging for 1 hour. Then, cooling was carried out down to 15C, taking 5 hours, being followed by aging at the temperature for 1hour. The obtained slurry was separated into a solid and a liquid, to obtain 172.1 g of a wet cake (pure 2-methylpiperazine content = 44.78 g = 0.447 mole) (optical purity = 92.6%ee, S-isomer yield = 86.1% based on the amount of supplied S-isomer). Then, a 1-liter four-neck flask with a thermometer, stirrer and condenser was charged with 130.0 g of water, and 154.9 g of the obtained cake (pure 2-methylpiperazine content = 40.30 g = 0.402 mole) was added at room temperature. The temperature was raised up to 75 to 85C for dissolution, and seed crystals were added at 70C, being followed by aging for 1 hour, cooling down to 15C taking 5 hours and aging at the temperature for 1 hour. The obtained slurry was separated into a solid and a liquid, to obtain 107.0 g of a wet cake (pure 2-methylpiperazine content = 36.40 g = 0.363 mole) (optical purity = 99.5%ee, S-isomer yield = 90.3% based on the amount of supplied S-isomer). Then, a 1-liter four-neck flask with a thermometer, stirrer and condenser was charged with 300 g of water, and 100.0 g of the obtained wet cake (pure 2-methylpiperazine content = 34.01 g = 0.340 mole) was added. The temperature was raised up to 70C for dissolution, and 34.42 g (0.442 mole, 1.3 molar times) of 95% calcium hydroxide was added. Aging was carried out at 78 to 82C for 3 hours, and solid-liquid separation was carried out to recover (S)-2-methylpiperazine. The 2-methylpiperazine content in the mother liquor was 33.38 g (= 0.333 mole) (recovery rate 98.0%). From the obtained mother liquor, 230 g of water was distilled away, and 340 g of 1-butanol was added, concentration then being carried out at 60 to 70C. In this case, Dean and Stark was installed to return the upper layer of the distillate into the distiller. When the water content in the distiller became 2.1 wt%, concentration was stopped, being followed by cooling down to 0C. The 2-methylpiperazine content of the solution in the distiller was 32.38 g (= 0.323 mole) (recovery rate = 97.0%). To the solution, 58.72 g (= 0.339 mole, 1.05 molar times) of benzyl chlorocarbonate was added dropwise while the dropwise added amount was adjusted to keep the temperature in the distiller at 0 to 10C. Then, the temperature was raised to room temperature, being followed by aging for 2 hours, and concentration under reduced pressure was carried out at 60 to 70C for distilling away 180 g (pure ZMP content = 68.50 g = 0.292 mole, reaction yield 90.5%). Three hundred and eighty grams of toluene was added, and concentration under reduced pressure was carried out at 60 to 70C, for distilling away 340 g. To the concentrate, 200 g of water was added, and 35% hydrochloric acid water was used to adjust the pH to 1.2. Aging was carried out for 30 minutes, and the upper layer was removed. The same operation was repeated further twice, and 48% sodium hydroxide aqueous solution was used to adjust the pH of the reaction solution to 12.0, being followed by addition of 140 g of toluene and stirring for 30 minutes. The lower layer was then removed, and 100 g of water was added, being followed by stirring. The lower layer was then removed, and the upper layer was concentrated under reduced pressure at 60 to 70C, toluene being then distilled away at 1.3 kPa and 80C, to obtain 67.60 g of a concentrate. The obtained compound was analyzed. As a result, the intended 1-benzyloxycarbonyl-3-methylpiperazine accounted for 97.2 liquid chromatography area %. The impurities showed 0.27 liquid chromatography area % for benzyl alcohol, 0.02 liquid chromatography area % for 1-benzyl-4-benzyloxycarbonyl-2-methylpiperazine, 0.01 liquid chromatography area % for 1-benzyl-2-methylpiperazine and no detection for 1,4-dibenzyloxycarbonyl-2-methylpiperazine (2.44 liquid chromatography area % for solvent toluene). Therefore, the total of impurities was 0.31 liquid chromatography area %.
109-07-9, The synthetic route of 109-07-9 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; Toray Fine Chemicals Co., Ltd.; EP1548010; (2005); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics