Reaktion #67783

Reaktionsgleichung

2-fluoroisonicotinic acid

dry ice IPA

2-fluoro-4-iodoaniline

lithium bis(trimethylsilyl)amide

→

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

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONvia addition funnel
2. 2
   Sonstigethe internal temp below −59° C. (˜2 h)
3. 3
   workup.ADDITIONAfter final addition
4. 4
   SonstigeThe 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
   SonstigeThe aqueous layer was separated
8. 8
   Extraktionthe organics were again extracted with base (1000 mL)
9. 9
   SonstigeA yellow solid precipitated
10. 10
    Filtrationwhich was filtered
11. 11
    WaschenThe resultant yellow cake was washed with water (2×400 mL)
12. 12
    Sonstigedried under high vacuum at 40° C. (17-19 g)
13. 13
    Sonstige5.2 min

Vorschrift

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)].

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