反应详情

A toluene solution of (+)(1S,2R,3S)]-3-[2-(2-hydroxyeth-1-yloxy)-4-methoxyphenyl]-1-(3,4-methylendioxyphenyl)-5-(prop-1-yloxy)indane-2-carboxylic acid (868.8 g @ 11.2% wt/wt, 192.5 mmol) was concentrated under reduced pressure to a volume of approximately 200 mL. Distillation was discontinued and 2-propanol (500 mL) was added to the concentrate. The organic solution was concentrated again under reduced pressure to a volume of approximately 200 mL. Distillation was discontinued and 2-propanol (500 mL) was added to the concentrate. The resulting solution in 2-propanol was allowed to stir at ambient temperature for approximately 15 minutes to obtain a homogeneous mixture then diluted with an additional 1000 mL of 2-propanol. The resulting solution was heated to approximately 60° C. over a period of 15-20 minutes under a gentle purge of nitrogen. Heating was discontinued and ethylene diamine (11.6 g, 99.5+%, 192.5 mmol) was added. The reaction mixture was cooled to 30-35° C. over a period of 4 hours. As the solution cooled to 57° C., precipitation of the title compound occurred. The resulting slurry was stirred at ambient temperature for approximately 12 hours then cooled to 0° C. an additional 3 hours before isolation of the title compound via filtration. The product was washed with 3 portions of 2-propanol (300 mL) followed by hexanes (600 mL) chilled to 0-5° C. The product was dried in the vacuum oven for approximately 16 hours at 20-25° C. to afford 91.6 g. (87%) of the title compound.

1. distillationDistillation
2. addition2-propanol (500 mL) was added to the concentrate
3. concentrationThe organic solution was concentrated again under reduced pressure to a volume of approximately 200 mL
4. distillationDistillation
5. addition2-propanol (500 mL) was added to the concentrate
6. customto obtain a homogeneous mixture
7. temperatureThe resulting solution was heated to approximately 60° C. over a period of 15-20 minutes under
8. customa gentle purge of nitrogen
9. temperatureHeating
10. temperatureThe reaction mixture was cooled to 30-35° C. over a period of 4 hours
11. temperatureAs the solution cooled to 57° C.
12. customprecipitation of the title compound
13. stirringThe resulting slurry was stirred at ambient temperature for approximately 12 hours
14. temperaturethen cooled to 0° C. an additional 3 hours before isolation of the title compound via filtration
15. washThe product was washed with 3 portions of 2-propanol (300 mL)
16. temperaturechilled to 0-5° C
17. customThe product was dried in the vacuum oven for approximately 16 hours at 20-25° C.
18. customto afford 91.6 g