C[O:2][C:3](=[O:17])[C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[C:6]([CH3:11])[C:5]=1[O:12][CH:13]1[CH2:16][CH2:15][CH2:14]1.O1CCOCC1.CO.[Li+].[OH-]>CO.C(Cl)Cl.O>[Cl:10][C:8]1[CH:7]=[C:6]([CH3:11])[C:5]([O:12][CH:13]2[CH2:14][CH2:15][CH2:16]2)=[C:4]([CH:9]=1)[C:3]([OH:17])=[O:2]A 100 mL flask containing 5-chloro-2-cyclobutoxy-3-methyl-benzoic acid methyl ester (0.57 g, 2.23 mmol) is charged with 1,4-dioxane (4 mL) and MeOH (4 mL). A stirring bar is added and stirring is initiated. After dissolution, water (2 mL) is added followed by the LiOH (237 mg, 5.65 mmol). After 39 h, tlc analysis (silica, 10% MeOH/DCM) indicates that the starting material is completely consumed. The pH of the reaction mixture is carefully adjusted to pH 2 by slowly adding dilute aqueous HCl (3%, ˜6 mL). The contents of the flask are poured into a separatory funnel containing EtOAc (30 mL). The layers are separated. The aqueous layer is extracted with EtOAc (20 mL). The combined organic extracts are washed with water (20 mL) and brine (20 mL), dried over MgSO4, filtered and concentrated by pumping to constant weight to give 0.53 g of white solid.
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