Hydrochloric Acid → 5-Chloro-N-methyl-N-propyl-isophthalamic acid

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Reaction Steps

Dissolve commercially available 5-chloroisophthalic acid dimethyl ester (1.0 g, 4.37 mmol) in acetone (10 mL) and add a solution of NaOH (192 mg, 4.81 mmol) in methanol (2 mL). Stir 3 h and concentrate. Partition the residue between diethyl ether and water. Acidify the water layer to about pH=1 and collect the precipitate, 5-chloro-isophthalic acid monomethyl ester (675 mg, 72%). Dissolve 5-chloro-isophthalic acid monomethyl ester (459 mg, 2.13 mmol) in DMF (20 mL), add 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (513 mg, 2.67 mmol) and 1-hydroxybenzotriazole (360 mg, 2.67 mmol). Stir at room temperature 1 h and add methyl propylamine (584 mg, 8.0 mmol). Stir at room temperature 3 h, dilute with ethyl acetate, wash with 10% aqueous potassium carbonate, 0.1 N citric acid, 1 N lithium chloride and saturated aqueous sodium chloride and concentrate. Dissolve the residue in THF (30 mL) and add 1 N lithium hydroxide (10 mL, 10 mmol). Stir at room temperature 3 h and acidify to about pH=1 by addition of 1 N HCl. Extract with diethyl ether, dry (magnesium sulfate) and concentrate to give the title compound.

Provenance & Evidence