Ethanol → Ethyl 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate

3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid, (1.63 g, 8.4 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.49 g, 7.8 mmol), 1-hydroxybenzotriazole hydrate (1.05 g, 7.8 mmol), and 4-dimethylaminopyridine (0.43 g, 3.5 mmol), were dissolved in 40 mL of anhydrous dichloromethane under argon. Triethylamine (4.0 mL, 29 mmol) was added to the room temperature mixture via syringe. Absolute ethanol (0.83 mL, 14.2 mmol) was then delivered to the solution, which was maintained at room temperature for 18 hours. HPLC (Eclipse XDB-C18, 4.6×250 mm, 5 micron, 1-99% CH3CN/H2O with 0.1% trifluoroacetic acid) chromatogram indicated that all of the starting material (Rt=3.7 min) was gone and that a single new product had formed (Rt=5.5 min). The solvent was removed by rotary evaporation and the residue was dissolved in 200 mL of ethyl acetate. The organic layer was washed with water (3×50 mL), 10% hydrochloric acid solution (3×50 mL), and 50% sodium bicarbonate solution (3×50 mL). The organic phase was dried over Na2SO4, filtered and concentrated to give ethyl 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate (1.6 g, 7.2 mmol, 86%) as a yellow solid. MS (ES) m/e 221 [M+H]+.

1. customhad formed (Rt=5.5 min)
2. customThe solvent was removed by rotary evaporation
3. dissolutionthe residue was dissolved in 200 mL of ethyl acetate
4. washThe organic layer was washed with water (3×50 mL), 10% hydrochloric acid solution (3×50 mL), and 50% sodium bicarbonate solution (3×50 mL)
5. dry with materialThe organic phase was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated

ORD record

ord-c86da07c81c34a83a35de09437288689

Source dataset

uspto-grants-2008_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07432258B2