Sodium Bicarbonate → (2R*,3S*)-3-hydroxy-4-methyl-2-[(4-phenylphenyl)-methoxy-carbonylamino]-pentanoic acid

Participants

Reaction Steps

To a stirred diastereomeric mixture containing (2R*,3R*)- and (2R*,3S*)-2-amino-3-hydroxy-4-methyl-pentanoic acid (0.05 g, 0.34 mmol) and NaHCO3 (0.03 g, 0.34 mmol) in H2O (2.0 mL), at rt, the isomeric mixture containing (4-phenylphenyl)-methyl-2-pyridyl carbonate and (4-phenylphenyl)-methyl-2-oxopyridine-1-carboxylate (0.45 g, 1.48 mmol) [prepared as for example 17, step 1] in THF (2.0 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 (0.06 g, 50% over 2 steps), as a diastereoisomeric mixture (anti:syn=8:2), as an off-white solid, which was used in the next step without further purification. MS (ESI) m/z: 358 [M−H]+; (ESI) m/z: 356 [M−H]−. 1H NMR (DMSO-d6) δ 0.82 (d, J=6.55 Hz, 3H), 0.88 (d, J=6.92 Hz, 3H), 1.62-1.79 (m, 1H), 3.17 (dd, J=2.87, 9.15 Hz, 1H), 3.51 (d, J=9.16 Hz, 1H), 5.05 (s, 2H), 7.32-7.41 (m, 1H), 7.41-7.52 (m, 4H), 7.66 (td, J=1.74, 6.70, 7.42 Hz, 4H) (reported data refer to the major anti diastereoisomer).

Provenance & Evidence