تفاعل #67783

معادلة التفاعل

2-fluoroisonicotinic acid

dry ice IPA

2-fluoro-4-iodoaniline

lithium bis(trimethylsilyl)amide

→

3-[(2-fluoro-4-iodophenyl)amino]isonicotinic acid

المذيبات

THF

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONvia addition funnel
2. 2
   أخرىthe internal temp below −59° C. (˜2 h)
3. 3
   workup.ADDITIONAfter final addition
4. 4
   أخرىThe bath was not removed
5. 5
   workup.WAITAfter 4 days
6. 6
   workup.ADDITIONthe dark slurry was poured into a biphasic mixture of aqueous 2.0 N sodium hydroxide (1000 mL) and ethyl acetate (150 mL)
7. 7
   أخرىThe aqueous layer was separated
8. 8
   استخلاصthe organics were again extracted with base (1000 mL)
9. 9
   أخرىA yellow solid precipitated
10. 10
    ترشيحwhich was filtered
11. 11
    غسيلThe resultant yellow cake was washed with water (2×400 mL)
12. 12
    أخرىdried under high vacuum at 40° C. (17-19 g)
13. 13
    أخرى5.2 min

الإجراء التجريبي

A mixture of 2-fluoro-4-iodoaniline (20.0 g, 84.38 mmol) in dry THF (80 mL) was cooled to −67° C. (dry ice/IPA bath) under nitrogen, prior to slow addition of 1.0 M lithium bis(trimethylsilyl)amide (255 mL, 255 mmol) via addition funnel, at a rate that kept the internal temp below −59° C. (˜2 h). After final addition, the yellow-green slurry was stirred for 30 min and then treated with 2-fluoroisonicotinic acid (8.0 g, 56.69 mmol). The bath was not removed, but the contents were allowed to slowly warm to room temp. After 4 days, the dark slurry was poured into a biphasic mixture of aqueous 2.0 N sodium hydroxide (1000 mL) and ethyl acetate (150 mL). The aqueous layer was separated and the organics were again extracted with base (1000 mL). The pH of the two aqueous layers was adjusted to ˜2 with concentrated hydrochloric acid. A yellow solid precipitated, which was filtered. The resultant yellow cake was washed with water (2×400 mL) and dried under high vacuum at 40° C. (17-19 g). LC/MS [(5.2 min; 359 (M+1)].

المصدر