Ethyl Acetoacetate → HCID 54690189, compound

Temperature

0 °C

A slurry of 60% NaH (0.790 g, 19.7 mmol) in THF (50 mL) under a N2 atmosphere was cooled to 0° C. and treated with ethyl acetoacetate (2.51 mL, 19.7 mmol). The resulting solution was subsequently treated with n-BuLi (12.3 mL, 19.7 mmol) and stirred for 20 min. at 0° C. to provide an orange solution which was treated via cannula with a solution of 3-chloro-N-methoxy-N-methylbenzamide (2.50 g, 15.15 mmol) in THF (5.0 mL). The mixture was allowed warm to ambient temperature where it was stirred for 14 h before being quenched with 2.0N HCl. The product was extracted with ethylacetate (3×50 mL), the layers combined, dried with Na2SO4, and the solvent removed in vacuo. The residue was then treated with conc. H2SO4 (20 mL) and the resulting mixture stirred for 18 h at room temperature before being diluted with H2O (200 mL). The product was then extracted with ethylacetate (3×100 mL) being sure to collect all solids. The layers were then combined and diluted with acetone to provide a homogenous solution which was dried with Na2SO4. The solvent was then removed in vacuo and the resulting solid recrystallized from acetone-hexane to provide the title compound (1.33 g, m.p. 254°-256° C.). 1H NMR (400 MHz, DMSO-d6) δ 11.957 (bs, 1 H), 7.889 (t, 1 H, J=1.5 Hz), 7.839-7.813 (m, 1 H), 7.598-7.524 (m, 2 H), 7.876 (d, 1 H, J=2 Hz), 5.450 (d, 1 H, J=2 Hz).

1. customto provide an orange solution which
2. temperatureThe mixture was allowed warm to ambient temperature where it
3. stirringwas stirred for 14 h
4. custombefore being quenched with 2.0N HCl
5. extractionThe product was extracted with ethylacetate (3×50 mL)
6. dry with materialdried with Na2SO4
7. customthe solvent removed in vacuo
8. additionThe residue was then treated with conc. H2SO4 (20 mL)
9. stirringthe resulting mixture stirred for 18 h at room temperature
10. additionbefore being diluted with H2O (200 mL)
11. extractionThe product was then extracted with ethylacetate (3×100 mL)
12. customto collect all solids
13. additiondiluted with acetone
14. customto provide a homogenous solution which
15. dry with materialwas dried with Na2SO4
16. customThe solvent was then removed in vacuo
17. customthe resulting solid recrystallized from acetone-hexane

ORD record

ord-316713ffb0c54899b9cd4ea592d86aee

Source dataset

uspto-grants-1998_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05808062