Hydrochloric Acid → 2-(6-acetamidochroman-2-yl)acetic Acid

To the dark brown ethyl 6-acetamidochroman-2-ylacetate of Example 5 was added 3.5 L of methanol and 3.5 L of 1 N aqueous sodium hydroxide. After stirring the reaction mixture for 2 h at room temperature, the methanol was removed from the reaction mixture providing a dark, aqueous residue. The residue was transferred into a separatory funnel and extracted with 3×2 L of methylene chloride. Between each extraction step, the aqueous fraction was distilled to remove any organic solvent. The pH of the aqueous fraction was adjusted to about 2 with 2 N hydrochloric acid, affording a sticky, dark oil, which was separated. The acidic, aqueous fraction was extracted with 3×2 L of ethyl acetate. The ethyl acetate extracts and the dark oil were combined to form a homogenous solution. This solution was washed 2×2 L of brine and dried over 100 g of anhydrous sodium sulfate. Removing the ethyl acetate afforded a thick, blackish oil, which solidified overnight under vacuum. The dark brown solid was dissolved in saturated aqueous sodium bicarbonate to provide a black solution. The well-stirred, black solution was titrated with 3 N hydrochloric acid. At about pH 7.5, a black oil began to form on the walls of the flask. At about pH 7.0, more black oil formed, and the color of the solution changed from black to light yellow. The mixture was allowed to stand for about 5 min for the black oil to settle. The supernatant was decanted and acidified to about pH 2.0. The resulting white suspension was stirred for 30 min. The precipitate was filtered and dried at 50° C. under reduced pressure affording 350 g of 2-(6-acetamidochroman-2-yl)acetic acid as off-white crystals. The overall yield from 1347 g of 6-(tert-butyloxycarbonylamino)chroman-2-one from example 1 was 46.2%.