反应详情

Benzyl 5-[2′-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-methoxy-4′-(trifluoromethyl)biphenyl-3-yl]-6-methylpyridine-2-carboxylate (52 mg, 0.065 mmol), palladium/active carbon (10%, w/w) (25 mg) were mixed in ethanol (10 mL). The resulting mixture was degassed and subject to H2 under 45 psi at room temperature on a Parr shaker for 3 hours to complete the reaction. The reaction mixture was filtered through a pad of Celite (521). The filtrate was concentrated in vacuo to afford a light brown glass. The residue was purified by preparative reverse-phase HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with a MeCN/H2O gradient mixture. The appropriate fractions were pooled and evaporated into an aqueous residue. The resulting residue was further lyophilized to afford 5-[2′-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-methoxy-4′-(trifluoromethyl)biphenyl-3-yl]-6-methylpyridine-2-carboxylic acid. LCMS calc.=712.16; found=713.19 (M+1)+. 1H NMR signals are doubled because of atropisomerism 1H NMR (CDCl3, 500 MHz) δ 8.07 (s, 1H), 7.86 (s, 1H), 7.77 (s, 1H), 7.71-7.62 (m, 4H), 7.45-7.36 (m, 2H), 7.19-7.07 (m, 2H), 5.55 (d, J=7.0 Hz, 0.55H), 5.42 (d, J=7 Hz, 0.45H), 4.99 (d, J=13 Hz, 0.5H), 4.85 (d, J=12.5 Hz, 0.5H), 4.14 (d, J=13.5 Hz, 0.5H), 3.95 (d, J=13.5 Hz, 0.5H), 3.92-3.80 (m, 4H), 2.61, 2.58 (s, 3H), 0.58 (d, J=5.0 Hz, 1.35H), 0.49 (d, J=5.5 Hz, 1.65H).

1. customThe resulting mixture was degassed
2. customthe reaction
3. filtrationThe reaction mixture was filtered through a pad of Celite (521)
4. concentrationThe filtrate was concentrated in vacuo
5. customto afford a light brown glass
6. customThe residue was purified by preparative reverse-phase HPLC (Kromasil 100-5C18, 100×21.1 mm)
7. washeluting with a MeCN/H2O gradient mixture
8. customevaporated into an aqueous residue