Hydrochloric Acid → methyl 3-(S)-n-butyl-3-[2-(S)-carboxypyrrolidin-1-yl-carbonyl)-2-(S)-fluoropropionate

Participants

Reaction Steps

To methyl 3-(S)-n-butyl-3-[2-(S)-tert-butoxycarbonylpyrrolidin-1-ylcarbonyl)-2-(S)-fluoropropionate H-4 (4.3 mmol) was added 4 N HCl in dioxane (15 mL), the solution stirred for 2 h, then evaporated to dryness to afford 4.3 mmol of methyl 3-(S)-n-butyl-3-[2-(S)-carboxypyrrolidin-1-yl-carbonyl)-2-(S)-fluoropropionate H-5 (quant.). To H-5 (0.15 mmol) in dioxane (1 mL) was added an amine (0.15 mmol), DIEA (0.38 mmol), and HATU or similar coupling reagent (0.15 mmol) and the solution stirred for 8 h. The reaction was cooled to 0° C., aqueous 50% hydroxylamine was added (0.5 mL) and the reaction stirred for 4 h. The crude reaction mixture was then purified by preparative reverse-phase (C18) HPLC to afford N-hydroxy-3-(S)-n-butyl-3-[2-(S)-aminocarbonylpyrrolidin-1-yl-carbonyl)-2-(S)-fluoropropionamide H-6.

Provenance & Evidence