Acetic Acid → tert-Butyl 4-[(4-acetylpiperazin-1-yl)methyl]-6-methylpyridin-2-ylcarbamate

Participants

Reaction Steps

2-Chloro-6-methyl-pyridine-4-carbaldehyde (13-2, 0.609 g, 3.91 mmol), tert-butylcarbamate (0.550 g, 4.70 mmol), cesium carbonate (1.91 g, 5.87 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.036 g, 0.040 mmol) and Xantphos (0.068 g, 0.030 mmol) were stirred in 10 mL of anhydrous dioxane under N2. The reaction was heated to 80° C. and after 18 hours the reaction was cooled to room temperature. The mixture was diluted with water and extracted 3× with EtOAc. The extracts were dried over Na2SO4, filtered and concentrated. Purification by flash column chromatography afforded impure tert-butyl 4-formyl-6-methylpyridin-2-ylcarbamate. This aldehyde was dissolved in 2 mL of 1,2-dichloroethane. N-Acetylpiperazine (0.074 g, 0.58 mmol) was added followed by addition of 0.05 mL HOAc and NaBH(OAc)3 (0.122 g, 0.58 mmol). After 3 hours the reaction was quenched by the addition of half-saturated NaHCO3 (aq). The mixture was extracted 3× with DCM (dichloromethane) and the extracts were dried over Na2SO4, filtered and concentrated to afford the titled compound, 13-3. 1H NMR (CDCl3) δ 7.67 (s, 1H), 7.47 (s, 1H), 6.84 (s, 1H), 3.64 (t, 2H, J=4.9 Hz), 3.47 (m, 4H), 2.44 (m, 7H), 2.09 (s, 3H), 1.51 (s, 9H).

Provenance & Evidence