2-Fluorobenzylamine → tert-butyl (2R,5S)-5-({[(2-fluorobenzyl)carbamoyl]oxy}methyl)-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate

Participants

Reaction Steps

A mixture of tert-butyl (2R,5R)-5-(hydroxymethyl)-2-[2-(2-{[N-(methoxycarbonyl)-β-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate (Example 1, step 10) (1 eq) and CDI (2.05 eq.) was dissolved in dry Pyridine (0.04 M) and the resulting solution stirred under N2 at rt for 5 h and then at 49° C. for 0.5 h; then neat 2-fluorobenzylamine (6 eq.) was added and the resulting mixture further stirred at the same temperature for 12 h. The crude reaction mixture was diluted with EtOAc, washed with 5% aq. KHSO4 then sat. NaHCO3, dried over Na2SO4, filtered and concentrated. The residue was purified by automated silicagel flash chromatography system eluted with a gradient 0% to 5% MeOH in DCM, to afford title compound.

Provenance & Evidence