Lithium hydroxide, monohydrate → (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-phenylpropenoic acid

A mixture of (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-phenylpropenoic acid methyl ester (Example 212; 23 mg, 0.048 mmol) and lithium hydroxide monohydrate (6 mg, 0.144 mmol) in methanol/tetrahydrofuran/water (2:2:1; 0.25 mL) was stirred at room temperature for 17 h. An second portion of lithium hydroxide monohydrate (2 mg, 0.05 mmol) was added and the solution was stirred for an additional 4 h. The volatiles were removed in vacuo and the residue was taken up in a mixture of chloroform/methanol/water/acetic acid (150:30:10:6) and evaporated to dryness. The residue was re-dissolved in the same solvent mixture (1 mL) and applied to a silica gel column. The column was eluted with in turn with chloroform, chloroform/methanol/water/acetic acid (300:30:10:6) and chloroform/methanol/water/acetic acid (150:30:10:6). The appropriate fractions were combined, evaporated and then lyophilized to give (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-phenylpropenoic acid (9.5 mg, 43% yield) as a colorless powder.