Sodium Iodide → HCID 58882977, compound

Participants

Reaction Conditions

Reaction Steps

A stirring suspension of methyl 3-amino-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate (60 g, 0.23 mol) in i-PrOAc (400 mL) was heated to 30° C. and trifluoroacetic anhydride (35.3 mL, 0.254 mol) was added dropwise. The reaction mixture was stirred 15 min at 30° C.; then cooled to rt and quenched slowly with 0.6 M NaHCO3 solution (512 mL, 0.32 mol). The resulting biphasic mixture was separated and the organic phase was washed twice with water; then diluted with CH3CN (700 mL) and distilled to about half its initial volume. To the remaining solution (ca. 600 mL) was added K2CO3 (34.6 g, 0.255 mol), NaI (5.18 g, 34.6 mol) and 2-chloro-N,N-dimethylacetamide (26.1 mL, 0.254 mol) and the resulting mixture was heated to 80° C. for 3.5 h. The reaction was cooled to 60° C., diluted with MeOH (200 mL), heated at reflux for 2 h and then distilled to approximately half its original volume. The remaining mixture was cooled to 37° C. and water (650 mL) was added over 2 h with gradual cooling to 15° C. A precipitate formed which was collected by filtration and washed with water. Drying of the filter cake in a vacuum oven afforded the product as an off-white solid: 1H NMR (CDCl3) δ 8.56 (1H, br), 7.89 (1H, s), 7.12 (2H, dd, J=8.5, 5.5 Hz), 6.98 (2H, t, J=8.5 Hz), 6.68 (1H, s), 3.96 (3H, s), 3.93 (2H, s), 3.88 (2H, d, J=4.2 Hz), 3.02 (3H, s), 3.01 (3H, s).

Provenance & Evidence