1-Phenethylamine, (-)- → (R)-3-hydroxymethylheptanoic acid, (S)-1-phenylethylamide

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

ORD record

ord-926c4ed2580c413fa9b3dd0ef0c64052

Source dataset

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06897233B2