1,2-Dichloroethane → 5-Fluoro-4-hydroxy-3-[(S)-2-(2-oxo-2H-pyridin-1-yl)-propionylamino]-pentanoic acid tert-butyl ester

HRID 419679Notes

Reaction equation

[O:1]=[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]1[C@@H:8]([CH3:12])[C:9]([OH:11])=O.[C:13]([O:17][C:18](=[O:26])[CH2:19][CH:20]([NH2:25])[CH:21]([OH:24])[CH2:22][F:23])([CH3:16])([CH3:15])[CH3:14].C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C1C=CN=CC=1)C.C1COCC1>[C:13]([O:17][C:18](=[O:26])[CH2:19][CH:20]([NH:25][C:9](=[O:11])[C@@H:8]([N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]1=[O:1])[CH3:12])[CH:21]([OH:24])[CH2:22][F:23])([CH3:16])([CH3:14])[CH3:15]

Participants

Conditions

Temperature: 0 °C

Procedure

A stirred mixture of (S)-2-(2-Oxo-2H-pyridin-1-yl)-propionic acid (70 mg, 0.42 mmol), 3-Amino-5-fluoro-4-hydroxy-pentanoic acid tert-butyl ester (91 mg, 0.44 mmol), HOAt (63 mg, 0.46 mmol) and DMAP (59 mg, 0.48 mmol) and anhydrous THF (5 ml) was cooled to 0° C. then EDC (88 mg, 0.46 mmol) was added. The mixture was allowed to warm to room temperature during 16 h then concentrated under reduced pressure. The residue was purified by flash chromatography (3% methanol in ethyl acetate) to afford the title compound as a white foam (137 mg, 92%): 1H NMR (400 MHz, CDCl3) δ 1.3-1.5 (9H, 2×s), 2.5-2.7 (2H, m), 3.4-3.7 (1H, m), 3.9-4.6 (4H, m), 5.4-5.6 (1H, m), 6.2-6.3 (1H, m), 6.5-6.6 (1H, m), 7.1-7.6 (3H, m); 19F NMR (376 MHz, CDCl3) δ −230.14, −230.14, −230.17, −230.95, −231.07.

Workup

temperatureto warm to room temperature during 16 h
concentrationthen concentrated under reduced pressure
customThe residue was purified by flash chromatography (3% methanol in ethyl acetate)

Sources & evidence

ORD record: ord-209b3a3249744fb497a12ba5aeab9a2f
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093392B2

Reaction notes

Loading…