benzyl 2-oxopiperidine-1-carboxylate

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 14.6 g (48.1 mmol) benzyl 2,4-dioxo-1,3,8-triaza-spiro[4.5]decan-8-carboxylate (prepared from N-(benzyloxycarbonyl)piperidone by the method from J. Med. Chem. 1995, 38, 3772) in 250 ml dry ethanol were added 500 mg 10% Pd/C, and the mixture was filled into an autoclave. After stirring at 60° C. and 10 atm of hydrogen for 3 h no starting hydantoin could be detected by TLC. A precipitate had been formed which was redissolved by addition of 100 ml acetic acid. The catalyst was removed by filtration and the solution was concentrated in vacuo. Aqueous sodium bicarbonate solution was added until the mixture became a clear solution, and the title compound precipitated in two crops upon concentration in vacuo. the mixture was filled into an autoclave A precipitate had been formed which The catalyst was removed by filtration the solution was concentrated in vacuo Aqueous sodium bicarbonate solution was added until the mixture the title compound precipitated in two crops upon concentration in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 11.65 g (50 mmol) N-(benzyloxycarbonyl)piperidone (prepared from 4-piperidone and benzyl chloroformate according to Chem. Pharm. Bull. 1982, 30, 1084) and 7.2 g (50 mmol) benzylamine hydrochloride were dissolved in a mixture of 20 ml methanol and 10 ml water. The solution was kept at 0° C., while 15 ml of an aqueous solution of 3.26 g (50 mmol) potassium cyanide were added dropwise. After stirring overnight at room temperature a crystalline solid had been formed, which was collected by filtration. The filtrate was treated with a mixture of water and ether. The organic layer was separated and the aqueous layer extracted with ether. The combined organic layers were dried over sodium sulfate and added to the solid material. The title hydrochloride precipitated after treating with a saturated ethereal solution of hydrogen chloride, and it was isolated by filtration and dried in vacuo. were added dropwise had been formed which was collected by filtration The filtrate was treated with a mixture of water and ether The organic layer was separated the aqueous layer extracted with ether The combined organic layers were dried over sodium sulfate added to the solid material The title hydrochloride precipitated after treating with a saturated ethereal solution of hydrogen chloride it was isolated by filtration dried in vacuo

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: n-Butyllithium (2.5 M in hexanes; 12.11 mL, 30.26 mmol) was added dropwise to a cooled (−78° C.) solution of piperidin-2-one (2.50 g, 25.22 mmol) in THF (100 mL). The mixture was stirred at −78° C. for 2.5 h. A solution of benzyl chloroformate (7.20 mL, 50.44 mmol) in THF (30 mL) was added dropwise. The mixture was stirred at −78 PC for 2 h and then was allowed to warm to rt. Water was added (200 and the mixture was extracted with EtOAc (3×100 mL). The combined organics were washed with brine, dried (Na2SO4), and concentrated to dryness to afford 4.13 g (70%) of the desired product. ES-MS m/z 233.91 [M+H]+, HPLC RT (min) 2.76. The mixture was stirred at −78 PC for 2 h to warm to rt the mixture was extracted with EtOAc (3×100 mL) The combined organics were washed with brine dried (Na2SO4) concentrated to dryness

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 14.6 g (48.1 mmol) benzyl 2,4-dioxo-1,3,8-triaza-spiro[4.5]decan-8-carboxylate (prepared from N-(benzyloxycarbonyl)piperidone by the method from J. Med. Chem. 1995, a, 3772) in 250 ml dry ethanol were added 500 mg 10% Pd/C, and the mixture was filled into an autoclave. After stirring at 60° C. and 10 atm of hydrogen for 3 h no starting hydantoin could be detected by TLC. A precipitate had been formed which was redissolved by addition of 100 ml acetic acid. The catalyst was removed by filtration and the solution was concentrated in vacuo. Aqueous sodium bicarbonate solution was added until the mixture became a clear solution, and the title compound precipitated in two crops upon concentration in vacuo. the mixture was filled into an autoclave A precipitate had been formed which The catalyst was removed by filtration the solution was concentrated in vacuo Aqueous sodium bicarbonate solution was added until the mixture the title compound precipitated in two crops upon concentration in vacuo

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 14.6 g (48.1 mmol) benzyl 2,4-dioxo-1,3,8-triaza-spiro[4.5]decan-8-carboxylate (prepared from N-(benzyloxycarbonyl)piperidone by the method from J. Med. Chem. 1995, 38, 3772) in 250 ml dry ethanol were added 500 mg 10% Pd/C, and the mixture was filled into an autoclave. After stirring at 60° C. and 10 atm of hydrogen for 3 h no starting hydantoin could be detected by TLC. A precipitate had been formed which was redissolved by addition of 100 ml acetic acid. The catalyst was removed by filtration and the solution was concentrated in vacuo. Aqueous sodium bicarbonate solution was added until the mixture became a clear solution, and the title compound precipitated in two crops upon concentration in vacuo. the mixture was filled into an autoclave A precipitate had been formed which The catalyst was removed by filtration the solution was concentrated in vacuo Aqueous sodium bicarbonate solution was added until the mixture the title compound precipitated in two crops upon concentration in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 11.65 g (50 mmol) N-(benzyloxycarbonyl)piperidone (prepared from 4-piperidone and benzyl chloroformate according to Chem. Pharm. Bull. 1982, 30, 1084) and 7.2 g (50 mmol) benzylamine hydrochloride were dissolved in a mixture of 20 ml methanol and 10 ml water. The solution was kept at 0° C., while 15 ml of an aqueous solution of 3.26 g (50 mmol) potassium cyanide were added dropwise. After stirring overnight at room temperature a crystalline solid had been formed, which was collected by filtration. The filtrate was treated with a mixture of water and ether. The organic layer was separated and the aqueous layer extracted with ether. The combined organic layers were dried over sodium sulfate and added to the solid material. The title hydrochloride precipitated after treating with a saturated ethereal solution of hydrogen chloride, and it was isolated by filtration and dried in vacuo. were added dropwise had been formed which was collected by filtration The filtrate was treated with a mixture of water and ether The organic layer was separated the aqueous layer extracted with ether The combined organic layers were dried over sodium sulfate added to the solid material The title hydrochloride precipitated after treating with a saturated ethereal solution of hydrogen chloride it was isolated by filtration dried in vacuo