BENZYL 4-(AMINOCARBONYL)TETRAHYDRO-1(2H)-PYRIDINECARBOXYLATE

Benzyl-4-carbamoylpiperidine-1-carboxylate To a solution of piperidine-4-carboxamide (5 g, 39 mmol) and benzylchloroformate (5.54 mL, 39 mmol ) in a mixture of water (30 mL) and acetone (40 mL), NaOH 1 N (39 mL, 39 mmol) was added dropwise, while maintaining the pH between 6 and 8. The mixture was stirred at r.t. for 3 h; then acetone was evaporated and the resulting precipitate filtered and dried at 70°C under reduced pressure, giving 7.75 g of benzyl-4-carbamoylpiperidine-1-carboxylate (76percent).HPLC: RGeneral procedure: To a solution of the aldoxime or the amide (1.0 mmol) and Et3N (1.5mmol) in EtOAc (1 mL, 1 M) at r.t. was added XtalFluor-E8 (1.1 mmol)portionwise over ca. 2 min. The resulting solution was stirred at r.t.for 1 h. The reaction mixture was quenched with sat. aq Na2CO3 and extracted with CH2Cl2 (2 × 10 mL). The combined organic layers were washed with H2O and brine, dried (MgSO4), and concentrated under vacuum to afford the crude nitrile, which was purified by flash chromatography, if required.General procedure: A 0.2 M solution of the corresponding methyl ester in aq NH4OH (28-30%) was stirred at r.t. for 16 h. The solvent was evaporated to affordthe amide, which was, in some cases, purified by silica gel chromatography. The known amides 3, 33 5a, 34 5b, 6c 5h, 35 11a, 36 11b, 37 11c, 3611e, 38 11h, 4 11i, 39 11j, 39 13, 40 14, 41 20, 42 and 2343 were synthesized following the general procedure described above. Compound 5e was synthesized following the literature.44To a solution of piperidine-4-carboxamide (5 g, 39 mmol) and benzylchloroformate (5.54 mL, 39 mmol ) in a mixture of water (30 mL) and acetone (40 mL), NaOH 1 N (39 mL, 39 mmol) was added dropwise, while maintaining the pH between 6 and 8. The mixture was stirred at r.t. for 3 h; then acetone was evaporated and the resulting precipitate filtered and dried at 70C under reduced pressure, giving 7.75 g of (1) Isonipecotamide (19.4 g) and triethylamine (42 mL) were dissolved in dichloromethane (500 mL), and benzyloxy chlorocarbonate (24 mL) was added thereto under ice-cooling. The mixture was stirred at room temperature for 18 hr. The reaction mixture was added to saturated aqueous sodium hydrogencarbonate solution, and the mixture was extracted with chloroform. The extract was dried and concentrated under reduced pressure to give The following compound is obtained analogously to Example V:EXAMPLE VI 1-Benzyloxycarbonyl-piperid-4-yl-thiocarboxylic acid amide A solution of 8.7 g of Benzyl-4-carbamoylpiperidine-1-carboxylate To a solution of piperidine-4-carboxamide (5 g, 39 mmol) and benzylchloroformate (5.54 mL, 39 mmol) in a mixture of water (30 mL) and acetone (40 mL), NaOH 1N (39 mL, 39 mmol) was added dropwise, while maintaining the pH between 6 and 8. The mixture was stirred at r.t. for 3 h; then acetone was evaporated and the resulting precipitate filtered and dried at 70 C. under reduced pressure, giving 7.75 g of EXAMPLE V 1-Benzyloxycarbonyl-piperid-4-yl-carboxylic acid amide 39 ml of 1N sodium hydroxide solution are slowly added dropwise to a solution of 5.0 g of piperid-4-yl-carboxylic acid amide and 5.54 ml of benzylchloroformate in 30 ml of water and 40 ml of acetone so as to keep the pH constant at between 6 and 8. The mixture is stirred for one hour at ambient temperature. Then the acetone is evaporated off under reduced pressure and the precipitate is suction filtered and dried. Yield: 8.8 g (86% of theory), Rf value: 0.55 (silica gel; methylene chloride/methanol/conc. ammonia=9:1:0.1)

Molecular Weight:262.30
XLogP3:1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:262.13174244
Monoisotopic Mass:262.13174244
Topological Polar Surface Area:72.6
Heavy Atom Count:19
Complexity:319
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes