反应详情

温度

60 °C

[(3R)-6-Hydroxy-2,3-dihydro-1-benzofuran-3-yl]acetic acid (R)-2-amino-1,1-diphenylpropan-1-ol salt (100 g) and sulfuric acid (30.26 g) were added to methanol (120 mL), and the mixture was stirred at 60° C. for 2 hr. After allowing to cool to room temperature, the solvent was concentrated under reduced pressure. To the residue were added toluene (831 mL), tetrahydrofuran (415 mL) and 1M hydrochloric acid (500 mL), and the mixture was partitioned. The organic layer was washed with water (500 mL), 5% aqueous sodium hydrogen carbonate solution (500 mL) and water (500 mL). The organic layer was concentrated, and toluene (110 mL) was added to the residue. The mixture was heated to 50° C., dissolved, allowed to cool to room temperature, and solid precipitation was confirmed. Normal heptane (220 mL) was added, and the mixture was stirred at room temperature for 5 hr. After cooling to 5° C., the solid was collected by filtration, washed with a mixed solution (1:2, 24 mL) of toluene-normal heptane. The solid was dried at 50° C. under reduced pressure to give the title compound (45.19 g). 99.6% ee.

1. temperatureto cool to room temperature
2. concentrationthe solvent was concentrated under reduced pressure
3. additionTo the residue were added toluene (831 mL), tetrahydrofuran (415 mL) and 1M hydrochloric acid (500 mL)
4. customthe mixture was partitioned
5. washThe organic layer was washed with water (500 mL), 5% aqueous sodium hydrogen carbonate solution (500 mL) and water (500 mL)
6. concentrationThe organic layer was concentrated
7. additiontoluene (110 mL) was added to the residue
8. temperatureThe mixture was heated to 50° C.
9. dissolutiondissolved
10. temperatureto cool to room temperature
11. customsolid precipitation
12. additionNormal heptane (220 mL) was added
13. stirringthe mixture was stirred at room temperature for 5 hr
14. temperatureAfter cooling to 5° C.
15. filtrationthe solid was collected by filtration
16. washwashed with a mixed solution (1:2, 24 mL) of toluene-normal heptane
17. customThe solid was dried at 50° C. under reduced pressure