Dimethylformamide → (2S,4S)-N-[2-(4-Cinnamylpiperazin-1-yl)ethyl]-6-fluoro-2',5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a chilled mixture (less than -5° C.) of 4-(2-aminoethyl)-1-cinnamylpiperazine (10.0 g, 40.8 mmol), 1,8-diazabicyclo[5,4,0]-7-undecene (6.20 g, 40.8 mmol) and N,N-dimethylformamide (55.0 ml, 710 mmol) was added over 30 minutes a solution of (2S,4S)-6-fluoro-2',5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carbonyl chloride (Reference Example 1, 11.1 g, 37.1 mmol) in N,N-dimethylformamide (100.1 ml, 1.29 mol). After stirring the mixture for 15 hours at 25° C., the solvent was evaporated. The residue was chromatographed on silica gel, eluted with a mixture of AcOEtAcOEt/MeOH (9:1), and evaporated in vacuo to dryness to give a colorless oil of the desired compound (17.5 g, 92.6%).

Provenance & Evidence