Pyridine → 1,1-Diethyl 4-oxocyclohexane-1,1-dicarboxylate

(Kutsuma, T., Sugasawa, S., Tetrahedron, 3, 175 (1958).) To 100 mL of a pre-mixed solution of 10% (v/v) pyridine and acetic anhydride was added 4,4-bis(ethoxycarbonyl)heptanedioic acid (23.6 g, 78 mmol), and the resulting mixture heated at reflux in a pre-heated oil bath. The reaction was stirred for 3 hrs then cooled to room temperature and concentrated under reduced pressure. The resulting oil was azeotroped twice with CH2Cl2, then dissolved in 95% EtOH (300 mL) and water (300 mL) and treated with solid potassium carbonate (12.9 g, 93.6 mmol). The mixture was stirred for 16 hrs. The reaction was concentrated under reduced pressure to remove EtOH, and the remaining water layer was diluted to re-dissolve the solids, then extracted with Et2O (2×150 mL). The combined extracts were dried (MgSO4), filtered, and concentrated under reduced pressure, to afford the title compound (11.82 g, 48.8 mmol, 62.9% yield), as an amber oil. HPLC: 2.00 min (AP 74%); 1H NMR (500 MHz, CDCl3) δ ppm 4.24 (4H, q, J=7.12 Hz), 2.44 (4H, t, J=6.56 Hz), 2.37 (4H, t, J=6.41 Hz), 1.27 (6H, t, J=7.17 Hz).

1. temperaturethe resulting mixture heated
2. temperatureat reflux in a pre-heated oil bath
3. concentrationconcentrated under reduced pressure
4. customThe resulting oil was azeotroped twice with CH2Cl2
5. dissolutiondissolved in 95% EtOH (300 mL)
6. stirringThe mixture was stirred for 16 hrs
7. concentrationThe reaction was concentrated under reduced pressure
8. customto remove EtOH
9. additionthe remaining water layer was diluted
10. dissolutionto re-dissolve the solids
11. extractionextracted with Et2O (2×150 mL)
12. dry with materialThe combined extracts were dried (MgSO4)
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure

ORD record

ord-cf85d6b9c577481d8f1379a4b1961683

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08835411B2