2,6-Lutidine → (3R*,5S*)-3-Amino-5-{cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester

Participants

Reaction Steps

To a stirred, ice-cooled solution of (3R*,5S*)-3-tert-butoxycarbonylamino-5-{cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester (prepared from cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-amine analogously as described in Example 59A) (1.2 g, 1.7 mmol) in CH2Cl2 (8 ml), 2,6-lutidine (0.79 mL, 6.8 mmol) is added followed by dropwise addition of trimethylsilyl trifluoromethanesulfonate (0.92 mL, 5.1 mmol). The cooling bath is removed, and the mixture is stirred at RT for 2.5 h. The reaction mixture is diluted with CH2Cl2 and washed with saturated NH4Cl solution. The organic layer is dried over Na2SO4 and evaporated in vacuo to afford the title compound as a brownish solid, which is used without further purification for the next steps. MS: 607.5 [M+H]+; tR (HPLC, Nucleosil C18; 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 8 min, flow 1.5 ml/min): 6.05 min.

Provenance & Evidence