4-Methylmorpholine → HCID 68528398, Verbindung

Temperatur

-12 °C

2-Amino-6-fluorobenzoic acid (2.00 g, 12.89 mmol) was combined with 2-fluorophenylhydrazine hydrochloride (2.096 g, 12.89 mmol) and HOBt (3.949 g, 25.79 mmol) in dry THF (75 ml) and cooled to about −12° C. N-Methylmorpholine (2.835 ml, 25.79 mmol) was added, the mixture was stirred for 5 minutes, then EDC hydrochloride (2.66 g, 13.88 mmol) was added. The mixture was maintained at a temperature between −14 and −10° C. for 1 hour, then allowed to slowly warm to room temperature and stirred for 18 hours. The mixture was cooled to 0° C., then filtered through CELITE® (diatomaceous earth). The filtrate was diluted with EtOAc, treated with saturated NaHCO3 and the layers separated. The organic layer was washed twice with 50% saturated NaHCO3 and then dried over MgSO4 and concentrated. The resulting solid was triturated with dichloromethane, filtered, rinsed with a very small amount of dichloromethane and dried. The filtrate from the trituration was re-triturated with a small amount of dichloromethane, filtered, rinsed with a tiny amount of dichloromethane and dried. The filtrate was concentrated to dryness, triturated with a small amount of Et2O, filtered, rinsed with a tiny amount of ether and dried. The three solids were combined to afford a total of 2.182 g (64%) of 2-amino-6-fluoro-benzoic acid N′-(2-fluoro-phenyl)-hydrazide (Intermediate 44) as an off-white solid. MS (APCI): (M−1)=262.0.

1. temperatureThe mixture was maintained at a temperature between −14 and −10° C. for 1 hour
2. temperatureto slowly warm to room temperature
3. stirringstirred for 18 hours
4. temperatureThe mixture was cooled to 0° C.
5. filtrationfiltered through CELITE® (diatomaceous earth)
6. additionThe filtrate was diluted with EtOAc
7. additiontreated with saturated NaHCO3
8. customthe layers separated
9. washThe organic layer was washed twice with 50% saturated NaHCO3
10. dry with materialdried over MgSO4
11. concentrationconcentrated
12. customThe resulting solid was triturated with dichloromethane
13. filtrationfiltered
14. washrinsed with a very small amount of dichloromethane
15. customdried
16. customThe filtrate from the trituration was re-triturated with a small amount of dichloromethane
17. filtrationfiltered
18. washrinsed with a tiny amount of dichloromethane
19. customdried
20. concentrationThe filtrate was concentrated to dryness
21. customtriturated with a small amount of Et2O
22. filtrationfiltered
23. washrinsed with a tiny amount of ether
24. customdried

ORD-Eintrag

ord-14816216d11343e8a25a5a1ee59c18c7

Quelldatensatz

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07423054B2