1-Boc-4-cyanopiperidine

Chemical Properties

1-Boc-4-cyanopiperidine is a yellowish oil,it is flammable, it reacts with oxidizing agents.

Uses

Reactant for synthesis of:

• Aminomethylated fluoropiperidines
• Protein kinase B inhibitors
• GlyT1 inhibitors
• Piperidinecarboxylic acids via nitrilase-catalyzed enantioselective synthesis

Reactant for

• Replacement in CB2 receptor inhibitors
• Double addition reactions of methyllithium and n-butyllithium to unsaturated nitriles

Application

1-Boc-4-cyanopiperidine is an important intermediate mainly used in pharmaceuticals and organic synthesis.

Synthesis

The general procedure for the synthesis of N-Boc-4-cyanopiperidine from tert-butyl 4-carbamoylpiperidine-1-carboxylate is as follows: to a solution of ethyl acetate (EtOAc, 1 mL, 1 M) containing an aldoxime or amide (1.0 mmol) and triethylamine (Et3N, 1.5 mmol) was added batchwise to XtalFluor-E (1.1 mmol) at room temperature. ). The reaction mixture was stirred at room temperature for 1 hour. Subsequently, the reaction was quenched with saturated sodium bicarbonate (NaHCO3) solution and extracted with aqueous sodium carbonate (Na2CO3) and dichloromethane (CH2Cl2, 2 × 10 mL). The combined organic layers were washed sequentially with water and brine, dried over anhydrous magnesium sulfate (MgSO4) and concentrated under reduced pressure to give the crude product. If necessary, the crude product can be purified by fast column chromatography.

References

[1] Synthesis (Germany), 2015, vol. 47, # 23, p. 3758 - 3766
[2] Patent: WO2004/2483, 2004, A1. Location in patent: Page/Page column 21-22; 39-40
[3] Chemistry of Heterocyclic Compounds, 2009, vol. 45, # 12, p. 1503 - 1507
[4] European Journal of Medicinal Chemistry, 1984, vol. 19, # 2, p. 181 - 186
[5] Chemical and Pharmaceutical Bulletin, 2001, vol. 49, # 7, p. 822 - 829