反应详情

A mixture of (+/−)-4-butyldihydrofuran-2-one (3.9 g, 27.4 mmol), 2-hydroxypyridine (3.1 g, 32.9 mmol) and (S)-1-phenylethyl amine (7.8 mL, 60.3 mmol) in dry toluene (50 mL) was heated to reflux overnight. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (100 mL), washed with 1 N HCl (2×50 mL) and brine (50 mL), dried (Na2SO4), and concentrated. The residue was purified by flash column chromatography (silica gel, 8:2 EtOAc/hexanes) to afford two compounds as white solids. The first eluted fraction was (S)-3-hydroxymethylheptanoic acid, (S)-1-phenyl-ethylamide (2.8 g, 39%) which is used in Example 3. 1H NMR (CDCl3) δ 7.33 (m, 5H), 6.07 (bs, 1H), 5.11 (q, 1H), 3.63 (m, 1H), 3.48 (m, 1H), 3.29 (bs, 1H), 2.29 (m, 2H), 1.95 (m, 1H), 1.50 (d, 2H), 1.28 (m, 6H), 0.88 (t, 3H). MS(ES) m/e 264 [M+H]+. The second eluted fraction was the title compound (2.6 g, 36%). 1H NMR (CDCl3) δ 7.29 (m, 5H), 6.34 (bs, 1H), 5.09 (q, 1H), 3.64 (m, 1H), 3.57 (bs, 1H), 3.48 (m, 1H), 2.28 (m, 2H), 1.93 (m, 1H), 1.48 (d, 2H), 1.28 (m, 6H), 0.88 (t, 3H). MS(ES) m/e 264 [M+H]+.

1. temperaturewas heated
2. temperatureto reflux overnight
3. washwashed with 1 N HCl (2×50 mL) and brine (50 mL)
4. dry with materialdried (Na2SO4)
5. concentrationconcentrated
6. customThe residue was purified by flash column chromatography (silica gel, 8:2 EtOAc/hexanes)
7. customto afford two compounds as white solids