Diethyl (ethoxymethylene)malonate → HCID 15632053, compound

Temperature

-78 °C

To a solution of LDA (1.8 M in THF/heptane/ethylbenzene, 64.8 mL, 117 mmol) in THF (200 mL) at −78° C. was added 2,3-lutidine (10.6 mL, 93.3 mmol) in THF (62 mL) dropwise over 10 min. After stirring the mixture an additional 40 min at −78° C., diethyl ethoxymethylenemalonate (21.7 mL, 107 mmol) in THF (30 mL) was added slowly over 15 min. The mixture was warmed slowly to rt over 2.5 h. The resulting solution was quenched with saturated aqueous NH4Cl and extracted with CH2Cl2 (3×). The combined extracts were dried (Na2SO4) and concentrated. The intermediate was dissolved in o-xylene (93 mL) and heated to reflux for 16 h. After cooling to rt, the mixture was concentrated. Purification by silica gel chromatography eluting with 0-5% MeOH:CH2Cl2 afforded ethyl 9-methyl-4-oxo-4H-quinolizine-3-carboxylate as a yellow solid.

1. temperatureThe mixture was warmed slowly to rt over 2.5 h
2. customThe resulting solution was quenched with saturated aqueous NH4Cl
3. extractionextracted with CH2Cl2 (3×)
4. dry with materialThe combined extracts were dried (Na2SO4)
5. concentrationconcentrated
6. dissolutionThe intermediate was dissolved in o-xylene (93 mL)
7. temperatureheated
8. temperatureto reflux for 16 h
9. temperatureAfter cooling to rt
10. concentrationthe mixture was concentrated
11. customPurification by silica gel chromatography
12. washeluting with 0-5% MeOH

ORD record

ord-c19d3e1829eb4588b7e115ceb219e64d

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08258135B2