1-CBZ-(S)-3-METHYLPIPERAZINE

1-CBZ-(S)-3-METHYLPIPERAZINE Property

Boiling point:

167°C 1mm

Density 

1,1 g/cm³

refractive index 

1.5365

Flash point:

178°C

storage temp. 

2-8°C(protect from light)

pka

8.50±0.40(Predicted)

Appearance

Colorless to light yellow Liquid

optical activity

Consistent with structure

Safety

Risk Statements 

36/37/38

Safety Statements 

26-36

HS Code 

2933599590

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P321Specific treatment (see … on this label).

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

1-CBZ-(S)-3-METHYLPIPERAZINE Chemical Properties,Usage,Production

Uses

(S)-benzyl 3-methylpiperazine-1-carboxylate is a useful research chemical.

Synthesis

Example 4: To a 1 L four-necked round-bottomed flask equipped with a thermometer, condenser tube and stirring device were added 100.2 g (1.00 mol) of racemic 2-methylpiperazine, 90.0 g (0.600 mol) of D-tartaric acid, 170 g of water and 36.0 g (0.600 mol) of acetic acid. The mixture was heated to 72 °C and aged at this temperature for 2 hours. The amount of solvent was 1.69 times the weight of racemic 2-methylpiperazine. Subsequently, the mixture was cooled to 15 °C over 12 hours and the precipitated crystals were collected by filtration. The resulting crystals were dried under vacuum to give 114.0 g (0.456 mol) of diastereoisomeric salt with an optical purity of 93.25% ee. Based on the amount of S-isomer in racemic 2-methylpiperazine, the yield of S-isomer was 88.0%. Next, 190 g of water and 114.0 g of the above crystals (44.0 g of pure (S)-2-methylpiperazine) were added to a 500 mL flask. After complete dissolution at 80 to 85 °C, the solution was cooled to 15 °C over 5 hours. The precipitated crystals were collected by filtration and dried under vacuum to give 100.5 g of salt with an optical purity of 99.5% ee. Based on the amount of (S)-2-methylpiperazine in the supplied crystals, the yield of the S-isomer was 91.1%. To a 200 mL four-necked round-bottomed flask equipped with a thermometer, condenser tube, and stirring device were added 75 g of water, 25.1 g of (S)-2-methylpiperazine D-tartrate (0.100 mol, 99.5% ee optical purity), and 7.8 g (0.100 mol) of 95% pure calcium hydroxide. The slurry was heated to 70 to 80 °C, stirred for 3 hours and then cooled to room temperature. The undissolved solids were removed by filtration to obtain the mother liquor.GC analysis showed that the mother liquor contained 9.2 g (0.0918 mol) of 2-methylpiperazine in 91.8% yield.HPLC analysis showed that (S)-2-methylpiperazine was optically pure at 99.5% ee.Subsequently, the mother liquor was concentrated to about 50 wt% water content, and azeotropically dehydrated by the addition of 1 -butanol until the system's water content was below 1 wt%. (S)-2-methylpiperazine was isolated by reduced pressure distillation. Using optically pure (S)-2-methylpiperazine (optical purity 99.5% ee) obtained by the above method, the reaction was carried out under the same conditions as in Example 1. The reaction was stirred at 0 to 5°C for 2 hours and then at room temperature for 12 hours. Analysis of the reaction solution showed a yield of 84.6% (based on the amount of 2-methylpiperazine) of 1-benzyloxycarbonyl-3-methylpiperazine and an optical purity of 99.5% ee, with no decrease in optical purity observed.

References

[1] Patent: EP1548010, 2005, A1. Location in patent: Page/Page column 17
[2] Patent: WO2004/101546, 2004, A1. Location in patent: Page 24
[3] Patent: WO2006/40192, 2006, A1. Location in patent: Page/Page column 28