Citric Acid → Benzenebutanoic acid, beta-amino-alpha-hydroxy-, (R*,S*)-

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Reaction Conditions

Reaction Steps

To (2S,3S)-3-tert-butoxycarbonylamino-1-chloro-2-hydroxy-4-phenylbutane (4.91 g, (2S,3S):(2R,3S)=99.2:0.8) obtained in the same manner as in Reference Example 1 were added 2-propanol (24.6 ml) and water (2.0 ml). 4N Aqueous sodium hydroxide solution (6.1 ml) was then added, and the mixture was stirred at 4° C. for 3 hr. After the completion of the reaction, citric acid (0.525 g) dissolved in water (28.7 ml) was added. The reaction mixture was once heated to 27° C. and cooled to −10° C. over 5 hr. The mixture was stirred at −10° C. for 10 hr, and crystals of (2S,3S)-3-tert-butoxycarbonylamino-1,2-epoxy-4-phenylbutane were collected by filtration. The wet crystals were analyzed by HPLC and found to be (2S,3S):(2R,3S)=100:0. To the obtained wet crystals was added acetonitrile (3.0 ml) and then a solution of citric acid (3.15 g) in water (2.5 ml) was added. The mixture was stirred at 70° C. for 2 hr. The mixture was cooled to room temperature and adjusted to pH=7.0 with 8N potassium hydroxide solution. To this solution were added sodium hydrogencarbonate (3.44 g), TEMPO (0.0246 g) and potassium bromide (4.88 g) and 12% aqueous sodium hypochlorite solution (25.4 g) was added dropwise at room temperature over 1 hr. After the completion of the dropwise addition, the mixture was stirred for 3 hr and sodium hydrogensulfite (0.853 g) was added to the reaction mixture. To this solution was added 8N aqueous potassium hydroxide solution (8.2 ml) and the mixture was stirred at 90° C. for 18 hr. The reaction mixture was cooled to room temperature and analyzed by HPLC, and as a result, it was confirmed that (2R,3S)-3-amino-2-hydroxy-4-phenylbutyric acid (3.02 g, yield 94%) was obtained. The reaction mixture was then cooled to 0° C. and adjusted to pH=5.5 with 6N aqueous hydrochloric acid solution. The mixture was stirred at 0° C. for 1 hr and the resulting crystals were collected by filtration. The crystals were dried under reduced pressure to give (2R,3S)-3-amino-2-hydroxy-4-phenylbutyric acid as crystals (2.41 g, yield 75%).

Provenance & Evidence