Pyridine → Ethyl β-oxo-4-pyridinebutanoate

A solution of pyridin-4-yl-acetic acid hydrochloride salt (1.73 g 10 mmol) in CH2Cl2 (50 mL) was treated with triethylamine (2.09 mL, 15 mmol), followed by 1,1′-carbonyldiimidazole (2.43 g, 15 mol). After 4 h, the solution was added dropwise to a 0° C. solution of 2,2-dimethyl-[1,3]dioxane-4,6-dione (Meldrum's acid; 1.73 g, 12 mmol) and pyridine (1.63 mL, 20 mmol) in CH2Cl2 (50 mL). The reaction mixture was allowed to warm slowly to rt and was stirred for 18 h. The mixture was washed with H2O (2×), and the organic layer was dried and concentrated. The crude residue was dissolved in EtOH (100 mL) and heated at reflux for 4 h. The mixture was allowed to cool to rt and was concentrated. The residue was purified by chromatography (EtOAc/hexanes) to give the title compound (411 mg, 15%) as a pale yellow oil. MS (ESI): mass calcd. for C11H13NO3, 207.1; m/z found, 208.1 [M+H]+. 1H NMR (CDCl3): 8.57 (dd, J=4.4, 1.6, 2H), 7.16 (dd, J=4.4, 1.6, 2H), 4.20 (q, J=7.2, 2H), 3.88 (s, 2H), 3.51 (s, 2H), 1.28 (t, J=7.2, 3H).

1. washThe mixture was washed with H2O (2×)
2. customthe organic layer was dried
3. concentrationconcentrated
4. dissolutionThe crude residue was dissolved in EtOH (100 mL)
5. temperatureheated
6. temperatureat reflux for 4 h
7. temperatureto cool to rt
8. concentrationwas concentrated
9. customThe residue was purified by chromatography (EtOAc/hexanes)

ORD record

ord-40b365b00de74299a9202f0080f4577b

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08686142B2