Isoxepac

55453-89-9

55453-87-7

General procedure for the synthesis of 2-(11-oxo-6,11-dihydrodibenzo[b,e]oxazepin-2-yl)acetic acid from 2-[(4-carboxymethylphenoxy)methyl]benzoic acid: 2-[(4-carboxymethylphenoxy)methyl]benzoic acid (total amount) obtained in Step 4 was added to a 500 mL four-necked flask with 200 mL of chlorobenzene, 75.0 g ( 0.3753 mol) trifluoroacetic anhydride, and the reaction was stirred at about 20°C for 4 hours. Subsequently, 2.3 g (0.0162 mol) of boron trifluoride-ether complex was slowly added dropwise over 10 minutes at -10 to 0 °C and stirring was continued for 30 minutes. After completion of the reaction, the aqueous phase was separated and the organic layer was washed with 200 mL of water. The washed organic layer was added to 300 mL of aqueous solution with 7.2 g of sodium hydroxide dissolved in it and stirred for 30 minutes, and the aqueous phase was again separated. To the aqueous phase, 2.0 g of activated carbon was added and stirred for 30 minutes, then the activated carbon was removed by filtration through a Brinell funnel and the activated carbon was washed with 10 mL of water. The filtrate was combined with the wash solution, the temperature was maintained at about 40 °C, and a mixture consisting of 11.3 g (0.1876 mol) acetic acid with 50 mL of water was added dropwise over 30 minutes. After the dropwise addition, the mixture was cooled to 0 to 10 °C and the crystals were collected by filtration through a Brinell funnel and washed with 200 mL of water. The resulting crystals were dried under reduced pressure to afford 42.0 g of the target product 2-(11-oxo-6,11-dihydrodibenzo[b,e]oxazepin-2-yl)acetic acid in 96.4% yield (based on 2-[(4-carboxymethylphenoxy)methyl]benzoic acid) and 99.9% purity by HPLC.HPLC conditions:The chromatographic column was Inertsil ODS-5 μm ( 4.6 mm ID×15 cm); mobile phase was 0.02% aqueous trifluoroacetic acid/acetonitrile=5/5→3/7 (30 min); detection wavelength was UV 254 nm. Physical property data: 1H NMR (400 MHz, DMSO-d6) δ 3.63 (s, 2H), 5.30 (s, 2H), 7.07 (d, J=8.0 Hz, 2H) , 7.48 (t, J=3.6 Hz, 1H), 7.55 (dd, J=7.9 Hz, 2H), 7.67 (t, J=7.6 Hz, 1H), 7.78 (d, J=7.6 Hz, 1H), 7.97 (d, J=2.0 Hz, 1H).