Diisopropylethylamine → (1R,2S)-ethyl 1-((2S,4R)-1-((S)-2-(tert-butoxycarbonylamino)-3-(pent-4-enyloxy)propanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate

Participants

Reaction Steps

(1R,2S)-ethyl-1-((2S,4R)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate hydrochloride salt (WO2005095403) (0.770 g, 2.45 mmol), (S)-2-(tert-butoxycarbonylamino)-3-(pent-4-enyloxy)propanoic acid (WO2004094452) (0.68 g, 2.50 mmol) and HATU (1.025 g, 2.696 mmol) in toluene (18 mL) and ACN (2 mL) was added DIEA (d 0.742) (1.281 mL, 7.352 mmol) at 0° C. The reaction warmed to rt and stirred at rt for 1 hr. Ethyl acetate (30 mL) and water (20 mL) was added. The organic layer was separated and washed with brine, dried over sodium sulfate. After removal of solvent, the residue was purified by chromatography (Ethyl acetate) to give (1R,2S)-ethyl 1-((2S,4R)-1-((S)-2-(tert-butoxycarbonylamino)-3-(pent-4-enyloxy)propanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate as white wax solid (0.92 g, 71.7%). MS: Calcd.: 523; Found: [M+H]+ 524.

Provenance & Evidence