With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.161609-84-3,Benzyl 4-cyanopiperidine-1-carboxylate,as a common compound, the synthetic route is as follows.
General procedure AF: Alkylation a to a nitrileA base such as LiHMDS, NaHMDS, KHMDS, LDA, NaH (1 to 5 equiv, preferably 1.5 equiv) is added to a nitrile compound in a suitable organic solvent such as THF, 1,4-dioxane, Et20, hexane, DMF, DMA (preferably THF) at about -78 C to rt (preferably about -78 C to 0 C) and stirred for 0.5 to 2 h (preferably about 1 h). An alkylating agent (1 to 5 equiv, preferably 1.5 equiv) is added and the mixture stirred for 30 min to 24 h (preferably about 16 h). To the mixture is is added an aqueous salt solution (preferably saturated NH4C1) and the mixture is extracted with a suitable organic solvent such as EtOAc, DCM, Et20 (preferably DCM). The organic layer is isolated and may be optionally washed in no particular order with water and/or aqueous solutions containing an acid (such as HC1, AcOH or NH4C1) and/or aqueous solutions containing a base (such as NaHC03, Na2C03, NaOH, KOH or NH4OH) and/or aqueous solutions containing an inorganic salt (such as NaCl Na2S03 or Na2S2C>3). The organic solution may then be optionally dried with a drying agent (such as anhydrous MgS04 or Na2S0 ), filtered and concentrated in vacuo to give the targeted compound. Alternatively, the residue obtained by concentration of the organic extracts may be purified by HPLC or column chromatography to provide the target compound.Illustration of General Procedure AF:Preparation No.AF.l: Benz l 4-cyano-4-methylpiperidine-l-carboxylateLiHMDS (47.6 mL, 47.6 mmol) was added dropwise via syringe to the mixture of benzyl 4- cyanopiperidine-l-carboxylate (8.00 g, 31.8 mmol, [Oakwood]) in THF (50 mL) at about -78 C and stirred for about 1 h. Mel (6.76 g, 47.6 mmol) was added dropwise via syringe at about -78 C and the mixture was stirred overnight at rt. The solution was cooled to 0 C and saturated aqueous NH4C1 (200 mL) was added. The mixture was extracted with DCM (3×300 mL). The combined organic extracts were dried over anhydrous Na2S04, filtered and concentrated in vacuo. The sample was deposited onto silica gel and purified by column chromatography eluting with 10: 1 pet ether/EtOAc to give benzyl 4-cyano-4-methylpiperidine-l-carboxylate (6.6 g, 74%): LC/MS (Table 2, Method i) Rt = 2.03 min; MS m/z: 259 (M+H)+.
161609-84-3 Benzyl 4-cyanopiperidine-1-carboxylate 22028286, apiperidines compound, is more and more widely used in various.
Reference£º
Patent; ABBOTT LABORATORIES; CALDERWOOD, David, J.; WILSON, Noel, S.; COX, Philip; HOEMANN, Michael, Z.; CLAPHAM, Bruce; MULLEN, Kelly, D.; VASUDEVAN, Anil; VILLAMIL, Clara I; LI, Bin; SOMAL, Gagandeep; WO2012/48222; (2012); A1;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem