Bromoacetyl bromide → 3-Oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid

Temperature

0 °C

3-amino-4-hydroxybenzoic acid (4.0 g, 26.0 mmol) was dissolved in 168 mL of chloroform. 92 mL of saturated sodium bicarbonate solution was added and the new bi-phase mixture was stirred vigorously and cooled to 0° C. using an ice bath. Bromoacetylbromide (3.42 mL, 39 mmol) was added drop-wise. Fifteen minutes later the solution was removed from the ice bath and maintained at room temperature for 48 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 was gone and a new peak (Rt=3.7 min) had formed. The reaction mixture was quenched using concentrated hydrochloric acid until the solution reached a pH of 2. The organic layer was separated and the aqueous phase was extracted with 100 mL of chloroform. The combined organic layers were treated with 75 mL of 10% hydrochloric acid solution and separated once again. The organic phase was dried over Na2SO4, filtered and concentrated to give 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid (4.8 g, 24.7 mmol, 95%) as an off-white amorphous solid. MS (ES) m/e 194 [M+H]+.

1. customFifteen minutes later the solution was removed from the ice bath
2. temperaturemaintained at room temperature for 48 hours
3. customa new peak (Rt=3.7 min) had formed
4. customThe reaction mixture was quenched
5. customThe organic layer was separated
6. extractionthe aqueous phase was extracted with 100 mL of chloroform
7. additionThe combined organic layers were treated with 75 mL of 10% hydrochloric acid solution
8. customseparated once again
9. dry with materialThe organic phase was dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated

ORD record

ord-5faa179d11614ae498a928bf29e88b77

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07749998B2