Lithium Hydroxide → 4-(2-Chloro-5-fluoro-benzoylamino)-3-methoxy-benzoic acid

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Reaction Steps

LiOH (14.1 g, 0.59 mol, 1.1 equiv.) dissolved in H2O (200 mL) was added drop-wise over 45 minutes to a solution of 34 (180 g, 0.53 mol, 1 equiv.) in tetrahydrofuran (1800 mL) at room temperature. The reaction mixture was stirred at room temperature for 16 h. The solvent was evaporated under reduced pressure and the residue re-dissolved in water (ca. 3 L). The insoluble solid was filtered off. Under vigorous stirring, the aqueous filtrate solution was acidified with concentrated HCl aqueous solution (37%) until pH<2. The resulting white solid precipitate was filtered and washed with water. The wet filter cake was then transferred to a flask and dried on rotary evaporator under vacuum at 50° C. overnight to yield 4-(2-chloro-5-fluoro-benzoylamino)-3-methoxy-benzoic acid 35 as a dry, fine white powder. 1H NMR (400 MHz, DMSO-d6) δ: 12.90 (s, 1H), 10.01 (s, 1H), 8.22 (d, 1H), 7.65-7.45 (m, 4H), 7.45-7.30 (m, 1H), 3.88 (s, 1H). MS (ES) m/z 322.0 (MH)+.

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