Sodium Hydroxide → 3-((2-Fluoro-4-iodophenyl)amino)isonicotinic acid

Temperature

-65 °C

A mixture of 2-fluoro-4-iodo-phenylamine (20.0 g, 84.38 mmol) in anhydrous tetrahydrofuran (80 mL) was cooled to −65° C. under an inert atmosphere, prior to slow addition of 1.0 M lithium bis(trimethylsilyl)amide (255 mL, 255 mmol) at a rate that maintained the internal temperature below −55° C. After final addition, the thick slurry was stirred for 30 minutes and then treated with 3-fluoro-isonicotinic acid (8.0 g, 56.69 mmol). The mixture was stirred at room temperature for 4 days and then poured into aqueous 2.0 N sodium hydroxide (1000 mL) and ethyl acetate (250 mL). The layers were separated and the organics were again extracted with aqueous sodium hydroxide (2×1000 mL). The pH of the combined aqueous fractions was adjusted to 2 with concentrated hydrochloric acid, which effected precipitation of a solid. The material was filtered, washed with water (300 mL) and dried under high vacuum at 40° C. for 18 h to afford the product (19.05 g, 53.19 mmol, 94%) as a yellow solid.

1. temperaturemaintained the internal temperature below −55° C
2. additionAfter final addition
3. stirringThe mixture was stirred at room temperature for 4 days
4. customThe layers were separated
5. extractionthe organics were again extracted with aqueous sodium hydroxide (2×1000 mL)
6. customprecipitation of a solid
7. filtrationThe material was filtered
8. washwashed with water (300 mL)
9. customdried under high vacuum at 40° C. for 18 h

ORD record

ord-5a0f0ef8d896476b8780ac4d9505e03a

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889719B2