Ethyl bromoacetate → [7-Methyl-6-(methyloxy)-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl]acetic acid

To a solution of 7-methyl-6-(methyloxy)-2H-1,4-benzoxazin-3(4H)-one (2.13 g, 11 mmol) in DMF (20 mL) was added NaH (528 mg, 13.2 mmol) in two portions. The reaction mixture was stirred for 30 minutes at room temperature, and ethyl bromoacetate (1.22 mL, 11 mmol) was added. The reaction mixture was stirred for 3 hour until all starting material was consumed, then poured into cold water (200 mL). The precipitate was collected by filtration, washed with water, and dried in the air to afford a pale solid. This solid was dissolved in THF (22 mL) and NaOH (2.0 M, 5.5 mL) was added, and the reaction mixture was stirred at room temperature for 2 h, poured into cold water (100 mL), and extracted with EtOAc (2×100 mL). The aqueous layer was acidified with HCl (6 N) to pH˜1, extracted with EtOAc (3×100 mL). The organic extracts were combined, washed with brine, and dried (Na2SO4). The solvent was removed via rotovap to give the title compound (2.35 g, 85%) as a pale solid. MS (ES) m/e 252 [M+H]+.

1. stirringThe reaction mixture was stirred for 3 hour until all starting material
2. customwas consumed
3. additionpoured into cold water (200 mL)
4. filtrationThe precipitate was collected by filtration
5. washwashed with water
6. customdried in the air
7. customto afford a pale solid
8. stirringthe reaction mixture was stirred at room temperature for 2 h
9. extractionextracted with EtOAc (2×100 mL)
10. extractionextracted with EtOAc (3×100 mL)
11. washwashed with brine
12. dry with materialdried (Na2SO4)
13. customThe solvent was removed via rotovap

ORD record

ord-7423fe59e363428a9626a2ae33415bdc

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07749998B2