1-Methylimidazole → HCID 86700559, compound

Participants

Reaction Steps

L-Alanine ethyl ester hydrochloride (0.50 g, 3.25 mmol) was suspended in 10 mL of CH2Cl2 and treated with phenyl phosphorodichloridate (0.50 mL, 3.35 mmol) at −10° C. and under an atmosphere of nitrogen. The well-stirred mixture was then treated dropwise with N-methylimidazole (1.0 mL, 12.5 mmol). After 1 hr. and still at −10° C., ethyl pantothenate (0.70 g, 2.8 mmol) in 3 mL of CH2Cl2 was added slowly. This mixture was allowed to warm to room temperature, and after 3 hrs, 2 mL of methanol was added. Extraction was performed sequentially with 1 M HCl, water, 5% NaHCO3, and brine. The organic phase was dried (Na2SO4), and the solvent was evaporated affording 1.11 g of a clear, colorless syrup. This material was purified by flash column chromatography using 30 g of silica gel and eluting with 1:1 EtOAc/hexanes containing 5% EtOH. The process was repeated until 1.1 g of phosphoramidate was obtained. HPLC showed the product, as a 1:1 mixture of disastereomers, having a purity of 97%. 1H NMR (300 MHz, CDCl3): δ 1.08 (s, 3H, CH3), 1.21 (d, 3H, J=2.7 Hz, CH3), 1.27 (m, 6H, CH3), 1.35 (t, 3H, J=6.9 Hz, CH3), 2.53 (q, 2H, J=4.2 Hz, CH2), 3.50 (m, 2H, CH2), 3.60 (m, 1H, CH), 3.78 (d, J=7.5 Hz, CH), 3.9 (m, 2H, CH2), 4.10 (m, 6H, CH2), 4.79 (t, 1H, J=6.5 Hz, CH), 7.15 and 7.40 (2 Ms, 5H, Ph). Expected Mol. Wt. 502.21, Observed Mol. Wt. 503.09 (M+H+]

Provenance & Evidence