Ethyl N-Boc-4-methylpiperidine-4-carboxylate Chemical Properties

Boiling point:

329.7±35.0 °C(Predicted)

Density 

1.0134 g/mL at 25 °C

refractive index 

1.4554

Flash point:

110 °C

storage temp. 

2-8°C

pka

-2.20±0.40(Predicted)

Appearance

Colorless to light yellow Liquid

Safety Information

Hazard Codes 

T

Risk Statements 

25-37/38-41

Safety Statements 

26-36/37/39-45

RIDADR 

UN 2810

WGK Germany 

3

HazardClass 

IRRITANT

Ethyl N-Boc-4-methylpiperidine-4-carboxylate Usage And Synthesis

Uses

Reactant for synthesis of:

• Dipeptidyl peptidase-4 inhibitor ABT-279
• Building blocks for piperazine-based CCR5 antagonists

Synthesis

Ethyl N-Boc-4-piperidinecarboxylate (10.00 g, 36.92 mmol) was dissolved in tetrahydrofuran (THF, 100 mL) and the solution was cooled to -78 °C. Under nitrogen protection, lithium diisopropylammonium (LDA, 47 mmol, 23 mL) was slowly added, maintaining the temperature at -78 °C, and the reaction mixture was stirred for 1 hour. Subsequently, iodomethane (81.25 mmol, 5.08 mL) was added dropwise and stirring was continued at -78 °C for 1 hour. Upon completion of the reaction, the cold bath was removed and the reaction mixture was allowed to warm slowly to room temperature and stirring was continued for 30 min. The reaction was quenched with saturated ammonium chloride (NH4Cl) solution followed by partition extraction with ethyl acetate (EtOAc). The organic phases were combined, dried with anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure to afford the target product ethyl N-Boc-4-methyl-4-piperidinecarboxylate in quantitative yield. The product was characterized by 1H NMR (400 MHz, DMSO-d6) with chemical shifts δ: 4.11 (q, J=7.1 Hz, 2H), 3.61 (dt, J=13.4 Hz, J=4.5 Hz, 2H), 2.95 (d, J=0.3 Hz, 2H), 1.91 (d, J=13.6 Hz, 2H), 1.39 (s, 9H) , 1.31 (m, 2H), 1.19 (m, 3H), 1.15 (s, 3H).

References

[1] Patent: WO2015/86527, 2015, A1. Location in patent: Page/Page column 113; 114
[2] Patent: WO2015/86525, 2015, A1. Location in patent: Page/Page column 117
[3] Patent: WO2008/121687, 2008, A2. Location in patent: Page/Page column 43; 89; 94
[4] Patent: WO2006/83003, 2006, A1. Location in patent: Page/Page column 36-37
[5] Journal of Medicinal Chemistry, 2017, vol. 60, # 11, p. 4680 - 4692

Ethyl N-Boc-4-methylpiperidine-4-carboxylate(189442-87-3)Related Product Information

• Triacetonediamine
• Ethyl acetate
• Urethane
• 1,2,2,6,6-Pentamethyl-4-piperidinol
• tert-Butyl carbazate
• Ethylparaben
• Ethanol
• Ethyl cyanoacetate
• Ethyl acrylate
• Ethyl 4-piperidinecarboxylate
• RESMETHRIN
• ISOXADIFEN-ETHYL
• Ethyl pyruvate
• 2,2,6,6-Tetramethyl-4-piperidinol
• Ethyl formate
• 4-(N-Boc-amino)phenylboronic acid pinacol ester
• Ethyl chloroformate
• 4-Methylpiperidine