Sodium Bicarbonate → (2R*,3S*)-3-hydroxy-4-methyl-2-(5-phenylpentoxy-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 (0.058 g, 0.4 mmol) and NaHCO3 (0.035 g, 0.4 mmol) in H2O (2.0 mL), at rt, the isomeric mixture containing 5-phenyl-pentyl-2-pyridyl-carbonate and 5-phenyl-pentyl-2-oxopyridine-1-carboxylate (0.38 g, 1.4 mmol) [prepared as for example 32, 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 (0.079 g, 59% 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: 338 [M−H]+; (ESI) m/z: 336 [M−H]−. 1H NMR (DMSO-d6) δ 0.81 (d, J=6.69 Hz, 3H), 0.88 (d, J=6.77 Hz, 3H), 1.32 (tt, J=5.81, 9.52 Hz, 2H), 1.57 (td, J=4.08, 8.39 Hz, 4H), 1.70-1.84 (m, 1H), 2.56 (t, J=7.71 Hz, 2H), 3.40 (t, J=6.09 Hz, 1H), 3.93 (t, J=6.61 Hz, 2H), 3.96-4.04 (m, 1H), 4.84 (s, 1H), 7.12-7.21 (m, 4H), 7.27 (t, J=7.49 Hz, 2H), 12.00-12.96 (s, 1H) (reported data refer to the major anti diastereoisomer).

Provenance & Evidence