反应详情

温度

22.5 °C

A suspension of 111.1 g of (R)-5-bromo-2-aminoindane (1S)-(+)-10-camphorsulfonate salt and 300 mL of isopropyl acetate is stirred at 20-25° C. and a solution of 15.0 g of sodium hydroxide and 75.0 g of sodium chloride in 300 mL of water is added over a period of 10 minutes while maintaining an internal temperature at 20 to 25° C. The suspension is stirred for 30 minutes or until all the solids dissolve. The organic layer is separated and the aqueous layer is extracted with 100 mL of isopropyl acetate. The organic layers containing (R)-5-bromo-2-aminoindane free base are combined. A solution of 60 g of sodium bicarbonate in 600 mL of water is added and the resulting white slurry is stirred under nitrogen and cooled to a temperature of 0-5° C. over a period of 15 minutes. A solution of 35.4 g of methyl chloroformate in 200 mL of isopropyl acetate is added over a period of 45 minutes while maintaining an internal temperature of 0-5° C. and the mixture is stirred at this temperature for an additional 1 hour. The organic layer is separated and washed with 150 mL of 1 N sulfuric acid is added, then with a solution of 10 g of sodium bicarbonate in 100 mL of deionized water and finally with 150 mL of deionized water. The organic layer is concentrated under vacuum (100-300 torr) at a temperature of 40-50° C. to ˜150 mL of a slurry. Heptane (500 mL) is added and the mixture is again concentrated under vacuum (100-200 torr) at a temperature of 40-50° C. to about 300 mL of a slurry. Heptane (500 mL) is again added and the mixture is cooled to an internal temperature of 0-5° C. The solid is collected and washed with 40 mL of heptane in two equal portions of 20 mL each. The solid is dried at 60-65° C. under vacuum (10-30 torr) to obtain (R)-(5-bromoindan 2-yl)-carbamic acid methyl ester as a crystalline white solid.

1. temperaturewhile maintaining an internal temperature at 20 to 25° C
2. stirringThe suspension is stirred for 30 minutes or until all the solids
3. dissolutiondissolve
4. customThe organic layer is separated
5. extractionthe aqueous layer is extracted with 100 mL of isopropyl acetate
6. additionThe organic layers containing (R)-5-bromo-2-aminoindane free base
7. additionA solution of 60 g of sodium bicarbonate in 600 mL of water is added
8. stirringthe resulting white slurry is stirred under nitrogen
9. temperaturecooled to a temperature of 0-5° C. over a period of 15 minutes
10. additionA solution of 35.4 g of methyl chloroformate in 200 mL of isopropyl acetate is added over a period of 45 minutes
11. temperaturewhile maintaining an internal temperature of 0-5° C.
12. stirringthe mixture is stirred at this temperature for an additional 1 hour
13. customThe organic layer is separated
14. washwashed with 150 mL of 1 N sulfuric acid
15. additionis added
16. concentrationThe organic layer is concentrated under vacuum (100-300 torr) at a temperature of 40-50° C. to ˜150 mL of a slurry
17. additionHeptane (500 mL) is added
18. concentrationthe mixture is again concentrated under vacuum (100-200 torr) at a temperature of 40-50° C. to about 300 mL of a slurry
19. additionHeptane (500 mL) is again added
20. temperaturethe mixture is cooled to an internal temperature of 0-5° C
21. customThe solid is collected
22. washwashed with 40 mL of heptane in two equal portions of 20 mL each
23. customThe solid is dried at 60-65° C. under vacuum (10-30 torr)