1-Hydroxybenzotriazole → ((S)-5-tert-butoxycarbonylamino-6-{(S)-2-[5-(4-fluoro-benzoyl)-pyridin-3-yl]-pyrrolidin-1-yl}-6-oxo-hexyl)-carbamic acid 9H-fluoren-9-ylmethyl ester

Participants

Reaction Steps

To a solution of (4-fluoro-phenyl)-((S)-5-pyrrolidin-2-yl-pyridin-3-yl)-methanone (1.0 g, 3.7 mmol), (S)-2-tert-butoxycarbonylamino-6-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid (2.0 g, 4.4 mmol) and ethyldiisopropylamine (3 mL) in DMF (20 mL) was added a solution of 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate (V) (1.67 g, 4.4 mmol) and 1H-benzo[d][1,2,3]triazol-1-ol (0.6 g, 4.4 mmol) in DMF (10 mL) and the mixture was shaken for 16 hours. The reaction mixture was diluted with ethyl acetate (300 mL), washed sequentially with brine (2×) (300 mL), saturated aqueous bicarbonate solution (300 mL), brine (300 mL), water (300 mL), and brine (300 mL), then dried over Na2SO4/MgSO4, and concentrated in vacuo to provide crude ((S)-5-tert-butoxycarbonylamino-6-{(S)-2-[5-(4-fluoro-benzoyl)-pyridin-3-yl]pyrrolidin-1-yl}-6-oxo-hexyl)-carbamic acid 9H-fluoren-9-ylmethyl ester as a light yellow foam.

Provenance & Evidence