Tetrahydrofuran → methyl 3-[3-amino-4-(indan-2-yloxy)-5-(1-methyl-1H-indazol-5-yl)phenyl]propionate

To methyl 3-[4-(indan-2-yloxy)-3-(1-methyl-1H-indazol-5-yl)-5-nitrophenyl]propionate (13.0 g), THF (138 ml), stabilized nickel (4.42 g, NIKKI CHEMICAL) and water (4 ml) were added, the mixture was stirred, then the interior of the system was purged with hydrogen, and the reaction was allowed under a hydrogen atmosphere at 50° C. for 7 hours with stirring. After confirming the completion of the reaction, the reaction solution was purged with nitrogen and filtered to obtain a filtrate, and the residue on the filter was washed with THF (34 ml) to obtain a wash solution. The filtrate and the wash solution were combined, activated carbon (2.6 g, Japan Envirochemical) was added to the combined solution, and the mixture was stirred for 1 hour at room temperature. The suspension was filtered to obtain a filtrate, and the residue on the filter was washed with THF (34 ml) to obtain a wash solution. Then, the resulting filtrate and the wash solution were combined, water (207 ml) was added to the combined solution over 1 hour, and the mixture was stirred for another 1 hour under ice cooling. Then, this mixture was filtered, and the solid on the filter was washed with water (68 ml) to obtain wet solid. This wet solid was dried under reduced pressure at 50° C. to obtain crystals of methyl 3-[3-amino-4-(indan-2-yloxy)-5-(1-methyl-1H-indazol-5-yl)phenyl]propionate (10.3 g).

1. additionwere added
2. customthe interior of the system was purged with hydrogen
3. stirringwith stirring
4. customthe completion of the reaction
5. customthe reaction solution was purged with nitrogen
6. filtrationfiltered
7. customto obtain a filtrate
8. washthe residue on the filter was washed with THF (34 ml)
9. customto obtain a wash solution
10. additionactivated carbon (2.6 g, Japan Envirochemical) was added to the combined solution
11. stirringthe mixture was stirred for 1 hour at room temperature
12. filtrationThe suspension was filtered
13. customto obtain a filtrate
14. washthe residue on the filter was washed with THF (34 ml)
15. customto obtain a wash solution
16. stirringthe mixture was stirred for another 1 hour under ice cooling
17. filtrationThen, this mixture was filtered
18. washthe solid on the filter was washed with water (68 ml)
19. customto obtain wet solid
20. customThis wet solid was dried under reduced pressure at 50° C.

ORD record

ord-600ba1e9f81c46609c44758f81927575

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09006225B2