(S)-(+)-2-Methylpiperazine

109-07-9

75336-86-6

74879-18-8

General procedure for the synthesis of (R)-(-)-2-methylpiperazine and (S)-2-methylpiperazine from 2-methylpiperazine: 1. In a 2L four-necked flask equipped with a thermometer, a vacuum stirrer and a cooling tube, 270 g (1.8 mol) of L-tartaric acid, 108 g (1.8 mol) of acetic acid and 270 g of water were added and stirred until completely dissolved. 2. add (±)-2-methylpiperazine 300 g (3.0 mol) and water 300 g. Heat to 85 °C or higher until completely dissolved. 3. cool to 68-74°C, add diastereomerically precipitated crystals of (R)-2-methylpiperazine and L-tartaric acid and age for 1 hour. 4. cooled to 12-18 °C over 5 h and filtered to obtain 440 g of wet biomass (diastereomeric salt) with a liquid content of 22.7 wt% and an optical purity of 92.3% ee. 5. 644 g of water and 440 g of the resulting crystals ((R)-2-methylpiperazine pure content = 132 g) were added to a 2L four-neck flask, followed by 162 g (2.2 mol) of calcium hydroxide, heated to 80 °C, and aged for 5 hours. 6. Cooled to 25 °C and filtered to give 586 g of crystals (mainly calcium L-tartrate) and 660 g of filtrate (containing 130 g of (R)-2-methylpiperazine). 7. The filtrate was concentrated under reduced pressure to a (R)-2-methylpiperazine concentration of 30%, 356 g of toluene was added, and the water was removed by azeotropic boiling by heating to 84-87 °C. 8. 212 g of toluene was distilled under reduced pressure, cooled to 47 °C, 0.01 g of (R)-2-methylpiperazine crystal seed was added and aged for 1 hour. 9. cooled to 5 °C, aged for 2 h, filtered and dried under vacuum to give 45 g of (R)-2-methylpiperazine crystals (chemical purity 100%, optical purity 99.5% ee). 10. For the synthesis of (S)-2-methylpiperazine, a similar procedure was used but with (S)-2-methylpiperazine as starting material, resulting in 66.8 g of (S)-2-methylpiperazine crystals (chemical purity 99.9%, optical purity 80.0%ee).