Isopropyl Acetate → 1H-Inden-2-amine, 5-bromo-2,3-dihydro-, (2R)-

To the above solution is added 1300 mL of isopropyl acetate and 930 mL of methanol. The solution is stirred under nitrogen and heated to an internal temperature of 65° C. to achieve a gentle refluxing, over a period of 15 minutes. A solution of 103.1 g of (1S)-(+)-10-camphorsulfonic acid in 660 mL of methanol is added over a period of 15 minutes while maintaining an internal temperature of 60-65° C. to obtain a clear solution followed by 185 mL of methanol to achieve a v/v ratio of isopropyl acetate:methanol of about 2:1. The reaction mixture is cooled to 20-23° C. over a period of 2 hours. The mixture is stirred at room temperature (20-23° C.) for an additional 2 hours. The solid is collected, washed with 500 mL of precooled (to 0-2° C.) mixture of isopropyl acetate and methanol (2:1; v/v) in two equal portions of 250 mL each, and dried at 50-55° C. (100 mm Hg) to obtain crude (R)-5-bromo-2-aminoindane (1S)-(+)-10-camphorsulfonate salt as a white solid. A mixture of 90.0 g of crude (R)-5-bromo-2-aminoindane (1S)-(+)-10-camphorsulfonate salt and 900 mL of methanol is heated to a temperature of 65° C. to achieve a gentle refluxing. This suspension is stirred at 65° C. for 1 hour and the reaction mixture is cooled to 20-23° C. over a period of 2 hours and stirred at 20-23° C. for an additional 2 hours. The resulting solid is collected, washed with 190 mL of precooled (to 0-2° C.) mixture of isopropyl acetate and methanol (1:1; v/v) in two equal portions of 95 mL each. The solid is dried at 50-55° C. (100 mm Hg) to obtain (R)-5-bromo-2-aminoindane (1S)-(+)-10-camphosulfonate salt as a white solid (98.7% optical purity).

1. temperaturewhile maintaining an internal temperature of 60-65° C.
2. customto obtain a clear solution
3. temperatureThe reaction mixture is cooled to 20-23° C. over a period of 2 hours
4. stirringThe mixture is stirred at room temperature (20-23° C.) for an additional 2 hours
5. customThe solid is collected
6. washwashed with 500 mL of precooled (to 0-2° C.) mixture of isopropyl acetate and methanol (2:1; v/v) in two equal portions of 250 mL each
7. customdried at 50-55° C. (100 mm Hg)
8. customto obtain crude (R)-5-bromo-2-aminoindane (1S)-(+)-10-camphorsulfonate salt as a white solid
9. temperatureis heated to a temperature of 65° C.
10. stirringThis suspension is stirred at 65° C. for 1 hour
11. temperaturethe reaction mixture is cooled to 20-23° C. over a period of 2 hours
12. stirringstirred at 20-23° C. for an additional 2 hours
13. customThe resulting solid is collected
14. washwashed with 190 mL of precooled (to 0-2° C.) mixture of isopropyl acetate and methanol (1:1; v/v) in two equal portions of 95 mL each
15. customThe solid is dried at 50-55° C. (100 mm Hg)

ORDレコード

ord-5376e43697ce46e58461d0f1e611be1a

出典データセット

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06878707B2