反应详情

温度

4 °C

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%).

1. additionwas added
2. temperatureThe reaction mixture was once heated to 27° C.
3. temperaturecooled to −10° C. over 5 hr
4. stirringThe mixture was stirred at −10° C. for 10 hr
5. filtrationcrystals of (2S,3S)-3-tert-butoxycarbonylamino-1,2-epoxy-4-phenylbutane were collected by filtration
6. additionTo the obtained wet crystals was added acetonitrile (3.0 ml)
7. additiona solution of citric acid (3.15 g) in water (2.5 ml) was added
8. stirringThe mixture was stirred at 70° C. for 2 hr
9. temperatureThe mixture was cooled to room temperature
10. additionTo 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)
11. additionwas added dropwise at room temperature over 1 hr
12. additionAfter the completion of the dropwise addition
13. stirringthe mixture was stirred for 3 hr
14. additionsodium hydrogensulfite (0.853 g) was added to the reaction mixture
15. additionTo this solution was added 8N aqueous potassium hydroxide solution (8.2 ml)
16. stirringthe mixture was stirred at 90° C. for 18 hr
17. temperatureThe reaction mixture was cooled to room temperature