Diisopropylethylamine → (3S*,5R*)-3-[Benzyl-(3-methyl-2-phenyl-butyl)-carbamoyl]-5-tert-butoxycarbonylamino-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester

Participants

Reaction Steps

To a stirred, ice-cooled mixture of (3S*,5R*)-5-tert-butoxycarbonylamino-piperidine-1,3-dicarboxylic acid 1-(9H-fluoren-9-ylmethyl) ester (466.5 mg, 1 mmol), benzyl-(3-methyl-2-phenyl-butyl)-amine (279 mg, 1.1 mmol) and N-ethyldiisopropylamine (1.37 mL, 8 mmol) in dimethylacetamide (6 mL), propylphosphonic anhydride solution (˜50% in DMF, 0.95 mL, ˜1.5 mmol) is added. The reaction mixture is stirred for 7 h at RT and evaporated in vacuo. The residue is dissolved in ethyl acetate and washed twice with an aqueous 10% K2CO3 solution. The organic layer is dried (Na2SO4) and evaporated in vacuo and the residue is purified by flash chromatography (hexane/ethyl acetate). The combined pure fractions are evaporated to afford the title compound as a white amorphous solid. MS: 702.3 [M+H]+; tR (HPLC, Nucleosil C18; 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 8 min, then 100% CH3CN+0.1% TFA for 2 min, flow 1.5 ml/min): 8.87 min.

Provenance & Evidence