Glycolic Acid → HCID 19008605, compound

Participants

Reaction Steps

To a dichloromethane solution (20 ml) of glycolic acid (0.3 g) and triethylamine (1.0 ml) was added an acid chloride (1.5 g) prepared as in Example 6 from 7-(2-chloro-6-fluoro-4-trifluoromethylphenoxy)-2,4-dimethyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazine-2-carboxylic acid (Compound 25), and the mixture was stirred at room temperature for one hour. The reaction mixture was then concentrated under a reduced pressure, the residue was extracted twice with ethyl acetate (20 ml), and the extract was washed with water and then with saturated aqueous sodium chloride, and dried over magnesium sulfate, followed by evaporation of the solvent under a reduced pressure to obtain carboxymethyl 7-(2-chloro-6-fluoro-4-trifluoromethylphenoxy)-2,4-dimethyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazine-2-carboxylate. The acid was dissolved in benzene (20 ml), thionyl chloride (0.9 g) was added thereto, and the mixture was heated under reflux for 3 hours. Then after an evaporation of the solvent under a reduced pressure, the residue was dissolved in dichloromethane (20 ml), ethylamine hydrochloride (0.6 g) and triethylamine (2 ml) were added thereto, and the mixture was stirred for one hour. The reaction mixture was then concentrated under a reduced pressure, and the residue was extracted twice with ethyl acetate (20 ml). The extract was washed with water and then with saturated aqueous sodium chloride, and dried over magnesium sulfate, followed by an evaporation of the solvent under a reduced pressure. The residue was purified by silica gel chromatography (eluant: n-hexane/ethyl acetate=3/1) to give 0.5 g of the title compound (colorless oil).

Provenance & Evidence