Methyl iodide → (S)-4-[(S)-4-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-1-hydroxymethyl-4-oxo-butyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid (3-chloro-4-trifluoromethoxy-phenyl)-methyl-amide

Participants

Reaction Steps

A solution of 0.02 ml (0.345 mmol) of iodomethane and 0.040 g (0.069 mmol) (S)-4-[(S)-4-(S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-1-hydroxymethyl-4-oxo-butyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid (3-chloro-4-trifluoromethoxy-phenyl)-amide (example 55) in 1.5 ml of acetonitrile was cooled (0° C.) and treated with 0.023 g (0.100 mmol) of silver(I) oxide. The reaction mixture was stirred at RT for 1 day, treated again with 0.02 ml (0.345 mmol) of iodomethane and stirred for 3 days. The reaction was partitioned between aqueous 10% KHSO4/EtOAc (3×). The organic phases were washed with aqueous saturated NaHCO3, aqueous 10% NaCl, dried (Na2SO4) and evaporated to give 0.040 g (88%) of the titled compound as off-white foam. MS: 591.22 (MH+, Cl).

Provenance & Evidence