[NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[OH:9].C([O:12][C:13](=[O:23])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20](O)=[O:21])C.[OH-].[Na+].Cl>C1(C)C=CC=CC=1.C(OCC)(=O)C.O.B(O)(O)O.NC1C=CC(C)=CN=1>[Cl:8][C:6]1[CH:5]=[CH:4][C:3]([OH:9])=[C:2]([CH:7]=1)[NH:1][C:20](=[O:21])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][C:13]([OH:23])=[O:12]8-(5-chloro-2-hydroxyanilino)-8-oxooctanoic acid was prepared as follows. A suspension of 2 amino-4-chlorophenol (17.88 g, 124.5 mmol), 8-ethoxy-8-oxo-octanoic acid (25.19 g, 124.5 mmol), boric acid (0.385 g, 6.23 mmol), and 2-amino-5-picoline (0.675 g, 6.23 mmol) in 160 mL of dried toluene was heated at reflux (110° C.) under nitrogen for 4 hours during which water (2.5 mL) produced in the reaction was removed by azeotropic distillation in a Dean-Stark separation unit. Thin layer chromatography on silica gel with an eluant of ethylacetate and heptane at a molar ratio of 1:1 indicated the completion of the reaction. The mixture was cooled and a 2N aqueous solution of sodium hydroxide (125 mL, 250 mmol) was added. The mixture was heated at reflux (about 85° C.) for 4 hours and cooled. The cooled mixture was diluted with ethyl acetate (300 mL) and water (150 mL). The aqueous layer was washed with two portions of ethyl acetate (250 mL). After careful separation, the aqueous layer was chilled and acidified with a 10% (by weight) solution of hydrochloric acid (86.20 mL, 250 mmol) to yield a solid. The solid was filtered, washed with hexane, and dried under vacuum. Trituration with dichloromethane yielded the 8-(5-chloro-2-hydroxyanilino)-8-oxooctanoic acid (22.39 g, 60%) as an off-white solid. HPLC (Column: Higgins Kromasil 100 C18, water/acetonitile/acetic acid: 950/50/1, 3 mL/min, 220 nm) Rt 5.38 min.; melting point 123-124° C.; 1H NMR(DMSO d6, 300 MHz)δ: 1.28(m, 4H), 1.51 (m, 4H), 2.19 (t, 2H), 2.39 (t, 2H),6.83 (d, 1H), 6.93 (dd, 1H), 7.95 (d, 1H), 9.20 (s, 1H), 10.10 (s, 1H), 12.00 (br s, 1H); 13C NMR (DMSO d6, 75 MHz) δ: 24.29, 24.90, 28.20, 33.58, 35.90, 116.50, 121.02, 122.20, 123.41, 127.74, 148.23, 171.93, 174.26. MS m/z 300 (M+1)+. Anal. Calcd for C14H18ClNO4: C, 56.10; H, 6.05; Cl, 11.83, N, 4.67. Found: C, 56.07, H, 6.11, 11.98, N, 4.64.
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