Tert-butyl 4-benzyl-3-oxopiperazine-1-carboxylate → Tert-butyl 4-benzyl-4,7-diazaspiro[2.5]octane-7-carboxylate

Participants

Reaction Conditions

Reaction Steps

To EtMgBr (344 mL) in THF cooled to −78° C. was added Ti(OiPr)4 (39 g, 137.93 mmol), followed by commercially available 4-benzyl-3-oxo-piperazine-1-carboxylic acid tert-butyl ester (40 g, 137.93 mmol) and the resultant reaction mixture was heated to reflux for 1 h. After cooling the reaction mixture to 5° C., another portion of EtMgBr (344 ml) and Ti(OiPr)4 (39 g, 137.93 mmol) was added. The mixture was stirred for 16 h at RT. The reaction mixture was quenched with NH4Cl solution and stirred for 15 min and filtered through a celite bed and washed with EtOAc. The aqueous layer was again extracted with EtOAc (3×). The combined EtOAc layers were washed with water and dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography to afforded the title compound as a solid (24 g, 58%).

Provenance & Evidence