1-BOC-ISONIPECOTIC ACID HYDRAZIDE

1-BOC-ISONIPECOTIC ACID HYDRAZIDE Property

Melting point:

104-106°C

Boiling point:

409.2±34.0 °C(Predicted)

Density 

1.147±0.06 g/cm3(Predicted)

storage temp. 

Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

form 

crystalline solid

pka

13.01±0.20(Predicted)

color 

White

InChI

InChI=1S/C11H21N3O3/c1-11(2,3)17-10(16)14-6-4-8(5-7-14)9(15)13-12/h8H,4-7,12H2,1-3H3,(H,13,15)

InChIKey

JLIKTOWFNQDEME-UHFFFAOYSA-N

SMILES

C1C(C(NN)=O)CCN(C(=O)OC(C)(C)C)C1

Safety

Hazard Codes 

Xi,Xn

Risk Statements 

22

HazardClass 

IRRITANT

HS Code 

2933399990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

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

P312Call a POISON CENTER or doctor/physician if you feel unwell.

P362Take off contaminated clothing and wash before reuse.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P501Dispose of contents/container to..…

1-BOC-ISONIPECOTIC ACID HYDRAZIDE Chemical Properties,Usage,Production

Uses

Ethyl N-Boc-4-piperidinecarboxylate is a key intermediate in the synthesis of sodium channel blockers used to treat stroke patients. It is also a key intermediate in the preparation of tumor necrosis factor converting enzyme inhibitors. Furthermore, it is a key intermediate in the synthesis of 1-BOC-4-piperidinecarboxylhydrazide.

Synthesis

The general procedure for the synthesis of 1-BOC-4-piperidinecarbohydrazide from ethyl N-Boc-4-piperidinecarboxylate is as follows: Example 4: Synthesis of tert-butyl 4-(hydrazinocarbonyl)piperidine-1-carboxylate 1. 10.0 g (38.9 mmol) of 4-tert-butyl 4-ethylpiperidine-1,4-dicarboxylate was dissolved in 35 mL of ethanol and 3.8 mL (3.90 g, 78 mmol) of hydrazine hydrate was added slowly under stirring conditions. 2. The reaction mixture was heated to reflux with continuous stirring for 9 hours. 3. Upon completion of the reaction, the mixture was cooled to room temperature, 1.9 mL (39 mmol) of hydrazine hydrate was added, and stirring was continued at reflux for 24 hours. 4. At the end of the reaction, the solvent was removed by concentration under reduced pressure and concentrated again by adding 50 mL of ethanol. 5. 150 mL of ether was added to the concentrate and the mixture was sonicated in an ultrasonic bath for 5 minutes. 6. The solid product was collected by filtration and dried to give 9.20 g of white solid in 97% yield. Product Characterization. LCMS (Method 6): Rt = 0.95 min, m/z = 244 (M+H)+ 1H-NMR (400 MHz, DMSO-d6): δ = 8.99 (s, 1H), 4.17 (br, 2H), 3.95 (br d, 2H), 2.71 (br, 2H), 2.23 (m, 1H), 1.60 (m, 2H), 1.40 (m, 11H).

References

[1] MedChemComm, 2018, vol. 9, # 12, p. 2083 - 2090
[2] Patent: US2011/144131, 2011, A1. Location in patent: Page/Page column 29
[3] Patent: WO2008/11130, 2008, A2. Location in patent: Page/Page column 151
[4] Journal of Medicinal Chemistry, 2008, vol. 51, # 15, p. 4430 - 4448
[5] Patent: WO2018/37223, 2018, A1. Location in patent: Page/Page column 147; 148