Sodium Hydroxide → HCID 13728676, compound

Participants

Reaction Steps

Methyl 4-amino-6-fluorochroman-4-carboxylate (11.5 g., 0.051 mole), the racemic spiro-amino acid methyl ester prepared in Example 20, was dissolved in 0.125M aqueous sodium chloride solution (100 ml.) at pH 5 by the addition of 6N hydrochoric acid. α-Chymotrypsin (750 mg.), available from the Sigma Chemical Company of St. Louis, MO., was then added to the mixture with stirring at room temperature (~20° C.). After an initial induction period of several hours, hydrolysis commenced as evidenced by the uptake of 0.5N aqueous sodium hydroxide from a pHstat to maintain the pH of the reaction solution at pH 5.1. The reaction was then continued until the uptake of base ceased. The reaction mixture was then acidified with 6N hydrochloric acid to pH 2 and activated carbon (1 g.) was added. After stirring for two hours, supercel (0.5 g.) was added and stirring was continued for another three hours. The spent reaction mixture was then filtered through supercel and extracted with ethyl acetate. The acqueous layer so obtained was adjusted to pH 10 with 6N aqueous sodium hydroxide and thereafter extracted with ethyl acetate (three times). The combined organic layers were then washed with brine and dried over anhydrous magnesium sulfate. After removal of the drying agent by means of filtration and the solvent by means of evaporation under reduced pressure, there were obtained 4.17 g. of pure (S)-methyl 4-amino-6-fluorochroman-4-carboxylate (73% yield based on available enantiomer) in the form of a colorless oil, [α]D25° +51.2° (c=0.64, CHCl3); NMR (CDCL3) identical with the racemic amino acid ester.

Provenance & Evidence