BENZENE ACETIC ACID, 4-[(2-CARBOXYPHENYL)METHOXY]

The intermediate I (3.2 kg, 10 . 2mol) and 34gTEBA into ethanol, stirring, by adding potassium hydroxide (1.2 kg, 21 . 4mol), heating reflow 3h, evaporate the ethanol, the residue for adding 20L water-soluble. Acidification with concentrated HCl to pH=1-2, generating a large amount of a buff solid, filtered, the filter cake is washed with water to neutral, buff solid obtained after drying 2.42 kg, II as intermediate, yield: 83.1percent.Production of (11-oxo-6, 11-dihydrodibenz[b, e]oxepin-2-yl)acetic acid The total amount of methyl 2-(4-methoxycarbonylmethylphenoxymethyl)benzoate obtained in was charged in a 4-neck flask, to which 150 ml of methanol and a solution of 17.0 g of sodium hydroxide dissolved in 100 ml of water were added, for agitation at 65°C for 2 hours. After the reaction mixture was cooled to room temperature (about 25°C), the reaction mixture was diluted with 200 ml of water, to which 2.0 g of active charcoal was added for agitation at room temperature for one hour. Subsequently, the resulting mixture was filtered through a Buchner funnel to remove the active charcoal. The active charcoal was washed on the Buchner funnel with 100 ml of water. The filtrate was combined with the wash water, which was then heated to 60°C. A solution of 26.5g of acetic acid dissolved in 50 ml of water was dropwise added to the heated solution over 2 hours, for depositing a crystal at the same temperature. After the solution was cooled to 10°C, then, the crystal was collected by filtration with a Buchner funnel, and washed with 200 ml of water. The crystal after washing was dried under reduced pressure, to obtain 46.5 g (0.1624 mole) of 2-(4-carboxymethylphenoxymethyl)benzoic acid. The yield (the yield from 4-hydroxyphenylacetic acid in Example 1) was 81.2 percent. Synthesis of the Intermediate 4-(2-Carboxybenzyloxy)Phenylacetic Acid (Olo-IM1) A solution of 4-hydroxyphenylacetic acid (90.0 g, 0.58 mol; assay >98percent) and phthalide (85.07 g, 0.63 mol) in DMF (323 g) was heated to an internal temperature of 130° C. The pressure was reduced to 800 mbar and sodium methoxide (224.6 g, 1.25 mol, assay: 30percent methanolic solution) was added slowly to the mixture maintaining the internal temperature above 100° C. During the addition methanol was distilled off, and after the addition the distillation was continued under normal pressure until the internal temperature increased to 130° C. again (260 g distillate). After stirring at this temperature for 6.5 h, phthalide (8.5 g, 0.06 mol) was added and the mixture was stirred overnight (16 h). Afterwards the mixture was cooled to 100° C. and hydrolyzed with water (1040 g). After cooling to <10° C., the pH of the mixture was adjusted to pH 1 with hydrochloric acid (163.5 g, 1.43 mol; assay: 32percent). The product was filtered off, washed with water (700 g) and dried under vacuum for 15 hours at 60° C. to give crude 4-(2-carboxybenzyloxy)phenylacetic acid (Olo-IM1) (yield: 174.6 g, 0.48 mol, 82.1percent; HPLC assay: 78.0percent). The crude Olo-IM1 (50.0 g, assay: 78.0percent, 0.14 mol) was recrystallized from acetonitrile/water (40 ml, 1/1). After filtration, the wet product washed successively with acetonitrile/water (98 ml, 1/1) and water (20 ml) to give slightly orange colored 4-(2-carboxybenzyloxy)phenylacetic acid (Olo-IM1) (yield: 35.27 g, 0.12 mol, 88.1percent; HPLC assay: 97.4percent; overall yield: 72.3percent).