Ethyl isocyanate → (S)-4-[(S)-1-Ethylcarbamoyloxymethyl-3-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-propyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-4-[(S)-3-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-1-hydroxymethyl-propyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester (intermediate 39; 63 mg, 0.14 mmol) in acetonitrile (1 mL) was added ethyl isocyanate (11 mg, 0.14 mmol) at 0° C. The ice bath was removed, then after 16 h another portion of ethyl isocyanate (11 mg, 0.14 mmol) was added, and the reaction mixture was stirred at 40° C. for 72 h. Volatile material was removed by concentration under vacuum, and the residue was chromatographed (SiO2; dichloromethane to dichloromethane/methanol/25% aq. ammonia solution 90:10:0.25) to afford the title compound (33 mg, 45%). Colorless gum, MS (ISP)=517.3 (M+H)+.

Provenance & Evidence