反应详情

A solution of (2R,4S)-4-amino-5-biphenyl-4-yl-2-methyl-pentanoic acid benzyl ester hydrochloride (100 mg, 0.287 mmol) and acetic acid (3S,4S)-4-acetoxy-2,5-dioxo-tetrahydro-furan-3-yl ester (0.431 mmol) in 1:1 methylene chloride/pyridine (1.4 mL) is stirred at room temperature for 24 hours. The solvents are removed under reduced pressure and obtained residue is used directly in the subsequent hydrolysis reaction. Next, a solution of the benzyl ester in ethyl acetate is hydrogenated at 1 atm over 10% Pd/C for 18 hours. Methanol is added and the catalyst is filtered through Celite. The Solvent is removed under reduced pressure and the residue is purified by preparative HPLC using a gradient of 10-100% MeCN/water (0.1% TFA). The proper fractions are lyophilized to furnish (2R,4S)-5-biphenyl-4-yl-4-((2S,3S)-2,3-diacetoxy-3-carboxy-propionylamino)-2-methyl-pentanoic acid. HPLC Retention time 0.95 minutes (condition A); MS 500.3 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.09 (d, J=7.20Hz, 3H), 1.45 (m, 1H), 1.82 (m, 1H), 2.39 (m, 1H), 2.70 (d, J=6.82Hz, 2H), 4.01 (m, 1H), 5.38 (m, 2H), 7.19 (d, J=8.21Hz, 2H), 7.34 (t, 1H), 7.45 (t, 2H), 7.53 (d, J=8.21Hz, 2H), 7.64 (d, J=7.20Hz, 2H), 8.00 (d, J=8.72Hz, 1H).

1. customThe solvents are removed under reduced pressure
2. customobtained residue
3. customis used directly in the subsequent hydrolysis reaction
4. filtrationthe catalyst is filtered through Celite
5. customThe Solvent is removed under reduced pressure
6. customthe residue is purified by preparative HPLC