Ethyl Acetoacetate → HCID 66747120, compound

A solution of 5-methyl-1H-benzo[d][1,3]oxazine-2,4-dione (Example 12c) (1.36 g, 7.68 mmol), ethyl 3-oxobutanoate (1.46 mL, 11.5 mmol), and NaOH (0.046 g, 1.15 mmol) in anhydrous dioxane (10 mL) were refluxed under nitrogen for 15 hrs. The solvent was then removed under vacuum, and the residue was re-dissolved in DMF (15 mL). To this solution was added POCl3 (1.41 mL, 15.4 mmol), and the reaction mixture was stirred at room temperature for 45 minutes. The reaction was carefully quenched with ice water (150 mL), and extracted with DCM (2×75 mL). The combined organic layers were washed with brine, and dried over Na2SO4. After evaporation of the solvent, the residue was purified by chromatography on silica gel eluting with 50% EtOAc in hexanes to give the title compound as red oil (520 mg, 26%). 1H NMR (400 MHz, DMSO-d6) δ 1.36 (t, J=7.6 Hz, 3H), 2.58 (s, 3H), 2.97 (s, 3H), 4.46 (q, J=7.6 Hz, 2H), 7.51 (d, J=7.2 Hz, 1H), 7.71 (m, 1H), 7.87 (d, J=7.6 Hz, 1H). MS 264, 266 (MH+)

1. customThe solvent was then removed under vacuum
2. dissolutionthe residue was re-dissolved in DMF (15 mL)
3. customThe reaction was carefully quenched with ice water (150 mL)
4. extractionextracted with DCM (2×75 mL)
5. washThe combined organic layers were washed with brine
6. dry with materialdried over Na2SO4
7. customAfter evaporation of the solvent
8. customthe residue was purified by chromatography on silica gel eluting with 50% EtOAc in hexanes

ORD record

ord-b1f7c5fe24a345da82f7d2faed885ceb

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09049878B2