4-Cyanopiperidine

Yellowish-Orangish Oil

Step A Preparation of mt 17-1 A solution of Boc-4-cyanopiperidine (4.00 g, 19.0 mmol) in 20 mL of HC1/EtOAc(4M) was allowed to stir at room temperature for 30 mm. The mixture was concentrated invacuo to provide 2.10 g of compound mt 17-1 as a white solid. Yield: 100percent. 1H-NMR (DMSO-d6) 9.32 (br, 1H), 3.183.O8 (m, 3H), 2.972.92 (m, 2H), 2.O82.O4 (m, 2H), 1.951.85 (m, 2H).A solution ofBoc-4-cyanopiperidine (4.00 g, 19.0 mmol) in 20 mL ofHCl/EtOAc10 (4M) was allowed to stir at room temperature for 30 min. The mixture was concentrated invacuo to provide 2.10 g of compound Int 17-1 as a white solid. Yield: 100percent. 1H-NMR(DMSO-d6) 8 9.32 (br, 1H), 3.18~3.08 (m, 3H), 2.97~2.92 (m, 2H), 2.08~2.04 (m, 2H), 1.95~1.85 (m, 2H).Step A Preparation of mt 17-1 10460] A solution of l3oc-4-cyanopiperidine (4.00 g, 19.0 mmol) in 20 mE of HC1/EtOAc (4M) was allowed to stir at room temperature for 30 mm. The mixture was concentrated in vacuo to provide 2.10 g of compound mt 17-1 as a white solid. Yield: 100percent. ‘H-NMR (DMSO-d6) ö 9.32 (br, 1H), 3.18-3.08 (m, 3H), 2.97-2.92 (m, 2H), 2.082.04 (m, 2H), 1.95-1.85 (m, 2H).A solution of Boc-4-cyanopiperidine (4.00 g, 19.0 mmol) in 20 mL of HCl/EtOAc (4M) was allowed to stir at room temperature for 30 min. The mixture was concentrated in vacuo to provide 2.10 g of compound Int 17-1 as a white solid. Yield: 100percent. 4-Pιperιdιnecarboxamιde (10 g, 78 mmol) was refluxed in thionyl chloride (35 mL) for 4 h until the suspension became homogeneous The reaction was cooled to rt and poured onto 300 g of crushed ice The ice slurry melted and the solution was treated with potassium hydroxide pellets until pH = 9 The reaction was concentrated to a residue which was partitioned between water and chloroform The aqueous layer was extracted with four portions of chloroform and the organic fractions were combined and concentrated The reaction yielded 3 1 g (36percent) of the 4- piperidmecarbonitrile as a brown oil Thionyl chloride 232 gm (molar ratio thionyl chloride:piperidine-4-carboxamide is 2.53:1) is taken in a 500 ml four-necked reaction flask, fitted with glass agitator and a condenser. A vent is provided at the condenser top passing through a 10percent diluted solution of caustic lye to neutralize the vent gases. Piperidine-4-carboxamide 100 gm is added lot wise with continuous stirring over a period of 30 minutes, temperature increased from 32° to 65° C. due to the exothermicity of the reaction. The reaction mixture is maintained at 65°-70° C. for 3-4 hours and a sample is drawn and analyzed, 4-cyanopiperidine 94.78percent Area, Piperidine-4-carboxamide=Nil is obtained. The reaction mass is cooled to room temperature and poured over 400 gm crushed ice by maintaining the temperature at 0°-10° C. Then, 160 gm (46percent solution) caustic lye is added to the above mass while maintaining the temperature between 15°-20° C. and the pH is adjusted between 12 and 13. The alkaline reaction mass is extracted with (400 ml.x.4) toluene. The organic layer is separated and the solvent is recovered by atmospheric distillation. The concentrated mass is distilled under high vacuum (4-6 mm Hg) to obtain 52.5 gm (molar yield=61percent) 4-cyanopipeiridne with purity 99.75percent. Thionyl chloride 70 gm (molar ratio, thionyl chloride:piperidine-4-carboxamide (1.50:1) is taken in a 250 ml 4-necked glass reactor fitted with an agitator and a condenser. A vent is provided at the condenser top passing through a 10percent diluted solution of caustic lye to neutralize the vent gases. Piperidine-4-carboxamide 50 gm is added lot wise and the same procedure as in is followed. 27 gm (molar yield 62.8percent) 4-cyanopiperidine is obtained after final distillation with purity 99.0percent. Thionyl chloride 465 gm (molar ratio, thionyl chloride:piperidine-4-carboxamide 10:1) is taken in a 500 ml, 4-necked glass reactor fitted with an agitator and a condenser. A vent is provided at the condenser top passing through a 10percent diluted solution of caustic lye to neutralize the vent gases. Piperidine-4-carboxamide 48 gm is added lot-wise and after following the same procedure as in Example 1, 13.5 gm (molar yield 32.7percent) of 4-cyanopiperidine is obtained with 98.75percent purity.

Molecular Weight:110.16
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:110.084398327
Monoisotopic Mass:110.084398327
Topological Polar Surface Area:35.8
Heavy Atom Count:8
Complexity:105
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes