反应详情

To a stirred diastereomeric mixture containing (2R*,3R*)- and (2R*,3S*)-2-amino-3-hydroxy-4,4-dimethyl-pentanoic acid (0.23 g, 1.38 mmol) and NaHCO3 (0.118 g, 1.4 mmol) in H2O (5.0 mL), at rt, the isomeric mixture containing 5-phenyl-pentyl-2-pyridyl-carbonate and 5-phenyl-pentyl-2-oxopyridine-1-carboxylate (0.57 g, 2.0 mmol) [prepared as for example 32, step 1] in THF (5.0 mL) was added. After 15 h at rt, the crude mixture was rotary evaporated to remove the organics and subsequently extracted with Et2O (3×10 mL). The aqueous phase was acidified with 2.0 M HCl solution to pH 2-3 and subsequently extracted with AcOEt (3×20 mL). The organic fraction was dried over Na2SO4, filtered and concentrated to dryness to afford the title compound (0.34 g, 70% over 2 steps), as a diastereoisomeric mixture (anti:syn=9:1), as an off-white solid, which was used in the next step without further purification. MS (ESI) m/z: 352 [M−H]+; (ESI) m/z: 350 [M−H]−. 1H NMR (DMSO-d6) δ 0.87 (s, 9H), 1.27-1.41 (m, 2H), 1.57 (q, J=7.46 Hz, 4H), 2.57 (t, J=7.70 Hz, 2H), 3.36 (t, J=7.52 Hz, 2H, under water signal), 3.85-4.15 (m, 3H), 7.13-7.32 (m, 5H), 7.32 (d, J=8.56 Hz, 1H), 11.91 (s, 1H) (reported data refer to the major anti diastereoisomer).

1. additionwas added
2. customthe crude mixture was rotary evaporated
3. customto remove the organics and
4. extractionsubsequently extracted with Et2O (3×10 mL)
5. extractionsubsequently extracted with AcOEt (3×20 mL)
6. dry with materialThe organic fraction was dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated to dryness