反应详情

To a solution of 10.31 g (3R,4R,5S)-4-acetylamino-5-tert.-butoxy-carbonyl-amino-3-(1-ethyl-propoxy)-cyclohex-1-enecarboxylic acid ethyl ester (25 mmol) in 100 ml ethyl acetate were added at room temperature. 25 ml 5N HC1 in ethyl acetate. After 20 min. a white precipitate was formed and the thick suspension was stirred at room temperature for 24 h. The suspension was diluted with 125 ml ethyl acetate, washed with ca. 40 ml 3N NaOH (pH ca. 9.5) and 50 ml 10% brine. The aqueous layers were extracted sequentially twice with 125 ml, a total of 250 ml ethyl acetate. The combined organic layers were dried (Na2SO4) and the solvent was removed by rotary evaporation (30° C./≧10 mbar) affording 8.06 g (3R,4R,5S)-4-acetylamino-5-amino-3-(1-ethyl-propoxy)-cyclohex-1-enecarboxylic acid ethyl ester which was dissolved in 50 ml ethanol and added over ca. 2h to a warm solution (55° C.) of 2.45 g 99% phosphoric acid (25 mmol) in 50 ml ethanol. (After the addition of ca. ⅔ of (3R,4R,5S)-4-acetylamino-5-amino-3-(1-ethyl-propoxy)-cyclohex-1-enecarboxylic acid ethyl ester, the clear solution was seeded with pure title product). After cooling down and stirring at 0-5° C. for 3 h, the suspension was filtered, washed twice with 40 ml, a total of 80 ml acetone and dried (50° C./10 mbar/16 h) affording 9,07 g (88.4%) white, crystalline title product, m.p. 201-202° C.