Reacción #67783

Ecuación de reacción

2-fluoroisonicotinic acid

dry ice IPA

2-fluoro-4-iodoaniline

lithium bis(trimethylsilyl)amide

→

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

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONvia addition funnel
2. 2
   Otrothe internal temp below −59° C. (˜2 h)
3. 3
   workup.ADDITIONAfter final addition
4. 4
   OtroThe 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
   OtroThe aqueous layer was separated
8. 8
   Extracciónthe organics were again extracted with base (1000 mL)
9. 9
   OtroA yellow solid precipitated
10. 10
    Filtraciónwhich was filtered
11. 11
    LavadoThe resultant yellow cake was washed with water (2×400 mL)
12. 12
    Otrodried under high vacuum at 40° C. (17-19 g)
13. 13
    Otro5.2 min

Procedimiento

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)].

Fuente