C-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine → (R)-1-[2-Hydroxy-3-(2-{[(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}-3,4-dioxocyclobut1-enylamino)benzoyl]pyrrolidine-2-carboxylic acid

Participants

Reaction Steps

494 mg (2.73 mmol) of C-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine in 3 ml of methanol were added to a solution of 500 mg (1.34 mmol) of (R)-1-[3-(2-ethoxy-3,4-dioxocyclobut-1-enylamino)-2-hydroxy-benzoyl]pyrrolidine-2-carboxylic acid in 47 ml of methanol at 50° C. After 3 days, 248 mg (1.37 mmol) of C-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine were added. After 4 days, the reaction medium was concentrated to dryness. The reaction medium was taken up in ethyl acetate and was washed with a saturated aqueous ammonium chloride solution and then with a 1 M aqueous solution of sodium dihydrogen phosphate. The organic phase was dried over magnesium sulfate, filtered and concentrated. The solid obtained was taken up, with stirring, in diethyl ether and a little ethyl acetate and was filtered. 400 mg of a beige solid were obtained. This solid was chromatographed on silica gel (ethyl acetate/acetone/water: 50/50/2 then 50/50/5). 240 mg were obtained in the form of a beige solid. Yield=35%, HPLC=52.43%+45.15% (mixture of the two diastereoisomers), Mp=198-205° C.

Provenance & Evidence