2,2-DIMETHYL-PIPERAZINE Chemical Properties

Boiling point:

155.2±8.0 °C(Predicted)

Density 

0.833±0.06 g/cm3(Predicted)

storage temp. 

Keep in dark place,Inert atmosphere,Room temperature

solubility 

Chloroform (Slightly), Methanol (Slightly)

pka

9.38±0.40(Predicted)

form 

Solid

color 

Pale Yellow Low Melting

InChI

InChI=1S/C6H14N2/c1-6(2)5-7-3-4-8-6/h7-8H,3-5H2,1-2H3

InChIKey

PIPWSBOFSUJCCO-UHFFFAOYSA-N

SMILES

N1CCNCC1(C)C

Safety Information

Hazard Codes 

Xi,N

Risk Statements 

42-51/53

Safety Statements 

61

RIDADR 

UN3077

2,2-DIMETHYL-PIPERAZINE Usage And Synthesis

Uses

2,2-Dimethylpiperazine is a chemical reagent used in the preparation of non-covalent NAAA inhibitors used as a protective agent for the development of multiple sclerosis.

Synthesis

Example 4 Synthesis of 2,2-dimethylpiperazine: 3,3-dimethylpiperazin-2-one (8.28 kg, 64.6 mol) was mixed with tetrahydrofuran (THF, 60 kg) and heated to 50-60 °C to form a slightly turbid solution. LiAlH4 (250 g, encapsulated in a soluble plastic bag) was slowly added to the stirring THF (50 kg) under nitrogen protection and a slow gas release was observed. After the gas release ceased, the addition of LiAlH4 (total 3.0 kg, 79.1 mol) was continued and the reaction was exothermic causing the temperature to rise from 22°C to 50°C. Subsequently, a solution of 3,3-dimethylpiperazin-2-one was added slowly and dropwise over a period of 2 h at 41-59 °C. The solution was then added to the suspension over a period of 2 h. The solution was then added to the suspension over a period of 1 h at 41-59 °C. After addition, the suspension was continued to be stirred at 59 °C (jacket temperature 60 °C) for 1 hour. After the reaction mixture was cooled, water (3 L) was added slowly over a period of 2 h. The temperature was controlled to be lower than 25 °C (cooling by EPO, jacket temperature 0 °C). Next, 15% aqueous sodium hydroxide solution (3.50 kg) was added over 20 min at 23 °C and cooled if necessary. Subsequently, water (9 L) was added within half an hour, cooling was required to maintain the temperature, and the mixture was stirred overnight under nitrogen protection. Celite filter (4 kg) was added, the mixture was filtered and the filter cake was washed with THF (40 kg). The filtrates were combined and concentrated in a reactor until the temperature in the reactor reached 70 °C (distillation temperature 66 °C, pressure 800 mbar). The residue (12.8 kg) was further concentrated by rotary evaporator to about 10 L. Finally, the mixture was fractionated at atmospheric pressure and the 163-164 °C fraction was collected to give 5.3 kg of product (72% yield). The structure of the product was confirmed by NMR.

References

[1] Patent: WO2005/16900, 2005, A1. Location in patent: Page/Page column 27-28
[2] Patent: WO2006/86986, 2006, A1. Location in patent: Page/Page column 15
[3] Patent: WO2006/86985, 2006, A1. Location in patent: Page/Page column 14-15
[4] Patent: WO2006/86984, 2006, A1. Location in patent: Page/Page column 20
[5] Patent: WO2015/38417, 2015, A1. Location in patent: Page/Page column 113; 114

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