Ethanamine, 2,2,2-trifluoro- → tert-butyl (2S,5S)-2-[(2-{[N-(tert-butoxycarbonyl)-4-fluoro-beta-(4-fluorophenyl)-L-phenylalanyl]amino}-6-fluorophenoxy)methyl]-5-[({[(2,2,2-trifluoroethyl)amino]carbonyl}oxy)methyl]morpholine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

tert-butyl (2S,5R)-2-[(2-{[N-(tert-butoxycarbonyl)-4-fluoro-β-(4-fluorophenyl)-L-phenylalanyl]amino}-6-fluorophenoxy)methyl]-5-(hydroxymethyl)morpholine-4-carboxylate (350 mg, 0.489 mmol) and CDI (159 mg, 0.978 mmol) in pyridine (4.89 mL) were heated to 60° C. for 30 min, LC/MS shows formation of desired intermediate. 2,2,2-trifluoroethylamine (1153 μl, 14.67 mmol) was then added and the reaction heated at 60° C. overnight (18 hours). LCMS shows complete conversion the next morning. The solvent was removed in vacuo and the residue was purified on silica gel (120 g), eluting with a gradient of 10-100% EtOAc/hexanes to afford the title compound (310 mg, 0.361 mmol, 74% yield) as a white foam, MS (ESI): m/z=841.4 (M+H); 98% pure by LC/MS.

Provenance & Evidence