1-Hydroxybenzotriazole → (S)-2-[[(S)-2-(Acetoxyacetyl)-1-pyrrolidinyl]carbonyl]-N-(phenylmethyl)-1-pyrrolidinecarboxamide

Participants

Reaction Steps

(S)-2-(Acetoxyacetyl)-1-(tert-butoxycarbonyl)pyrrolidine (8.9 g) was dissolved in trifluoroacetic acid-acetic acid (1:1 solution, 90 ml), and the mixture was stirred at room temperature for 1.5 hours. The reaction mixture was concentrated under reduced pressure and the residue was suspended in methylene chloride. The suspension was added to a solution of N-(benzylaminocarbonyl)-L-proline obtained by stirring L-proline (4.0 g), benzyl isocyanate (3.9 g) and triethylamine (3.5 g) in DMF (40 ml) at room temperature for 1 hour. Then, HOBt (4.7 g) and water-soluble carbodiimide hydrochloride (6.7 g) were added. The mixture was stirred at room temperature overnight and methylene chloride was added to the reaction mixture. The resulting mixture was washed with 10% potassium hydrogensulfate, a saturated aqueous solution of sodium bicarbonate and water in order, dried over anhydrous sodium sulfate, and concentrated. The residue was dissolved in ethyl acetate, added with active charcoal, stirred at room temperature for 30 minutes, filtered and concentrated to give the title compound (4.8 g) (see Table 1).

Provenance & Evidence