反应详情

温度

60 °C

Crude tert-Butylammonium 2-{[2-(4-hydroxyphenyl)ethyl]thio}-3-[4-(2-{4-[(methylsulfonyl)oxy]phenoxy}ethyl)phenyl]propanoate (11.7 g, 19.8 mmol) was stirred in warm absolute ethanol (53.8 mL) at 71° C. to achieve complete dissolution. The resulting solution was screened into a second vessel through a 1 μm filter, followed by a line wash of warm ethanol (4.7 mL), and the solution allowed to cool to 60° C. Seed crystals (60 mg, 0.5% w/w) were added as a slurry in ethanol (0.5 mL) and the solution held at 60° C. for 30 minutes before cooling to 51° C. at 0.1° C./minute. The solution was held at 51° C. for 3 hours, during which period further seed crystals formed. The slurry was cooled to 46° C. at 0.1° C./minute, and held for 3 hours; then to 41° C. at 0.1° C./minute, and held for 3 hours; then to 31° C. at 0.1° C./minute, and held for 2 hours; then to 17° C. at 0.17° C./minute, and held for at least 5-6 hours. The solid was isolated by filtration, washed by displacement with absolute ethanol (11.7 mL) and dried in a vacuum oven at 50° C. to yield the title compound as a white solid (10.2 g, 87%). HPLC (Rt 9.8 min); chiral HPLC (typically 98% e.e.); mp 137-139° C.; MS (ES+) 534 (M+NH4+, 20%), 517 (M+H+, 30%), 471 (M-CO2H+, 100%). Other data as noted for the Crude stage above.

1. dissolutiondissolution
2. customThe resulting solution was screened into a second vessel through a 1 μm
3. filtrationfilter
4. washwash of warm ethanol (4.7 mL)
5. additionSeed crystals (60 mg, 0.5% w/w) were added as a slurry in ethanol (0.5 mL)
6. temperaturebefore cooling to 51° C. at 0.1° C./minute
7. waitThe solution was held at 51° C. for 3 hours, during which period further seed crystals
8. customformed
9. temperatureThe slurry was cooled to 46° C. at 0.1° C./minute
10. waitheld for 3 hours
11. waitthen to 41° C. at 0.1° C./minute, and held for 3 hours
12. waitthen to 31° C. at 0.1° C./minute, and held for 2 hours
13. waitthen to 17° C. at 0.17° C./minute, and held for at least 5-6 hours
14. customThe solid was isolated by filtration
15. washwashed by displacement with absolute ethanol (11.7 mL)
16. customdried in a vacuum oven at 50° C.