تفاعل #58689

معادلة التفاعل

N-Methylmorpholine

2-Amino-6-fluorobenzoic acid

2-fluorophenylhydrazine hydrochloride

EDC hydrochloride

HOBt

→

2-amino-6-fluoro-benzoic acid N′-(2-fluoro-phenyl)-hydrazide

المردود 64.3%

المذيبات

THF

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe mixture was maintained at a temperature between −14 and −10° C. for 1 hour
2. 2
   درجة الحرارةto slowly warm to room temperature
3. 3
   workup.STIRRINGstirred for 18 hours
4. 4
   درجة الحرارةThe mixture was cooled to 0° C.
5. 5
   ترشيحfiltered through CELITE® (diatomaceous earth)
6. 6
   workup.ADDITIONThe filtrate was diluted with EtOAc
7. 7
   workup.ADDITIONtreated with saturated NaHCO3
8. 8
   أخرىthe layers separated
9. 9
   غسيلThe organic layer was washed twice with 50% saturated NaHCO3
10. 10
    تجفيفdried over MgSO4
11. 11
    تركيزconcentrated
12. 12
    أخرىThe resulting solid was triturated with dichloromethane
13. 13
    ترشيحfiltered
14. 14
    غسيلrinsed with a very small amount of dichloromethane
15. 15
    أخرىdried
16. 16
    أخرىThe filtrate from the trituration was re-triturated with a small amount of dichloromethane
17. 17
    ترشيحfiltered
18. 18
    غسيلrinsed with a tiny amount of dichloromethane
19. 19
    أخرىdried
20. 20
    تركيزThe filtrate was concentrated to dryness
21. 21
    أخرىtriturated with a small amount of Et2O
22. 22
    ترشيحfiltered
23. 23
    غسيلrinsed with a tiny amount of ether
24. 24
    أخرىdried

الإجراء التجريبي

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.

المصدر