Aniline → 2-Phenylamino-6-trifluoromethyl-nicotinic acid

Temperature

-78 °C

In a 50 mL round-bottomed flask, 2-chloro-6-(trifluoromethyl)-nicotinic acid (5 g, 22.2 mmol) was combined with THF (20 mL) to give a dark red solution. The reaction solution was cooled to −78° C., lithium hexamethyldisilazane (LiHMDS, 1.0 M in THF) (66.5 mL, 66.5 mmol) was added and stirred for 2 hr. A solution of aniline (19.6 g, 19.2 mL, 210 mmol) in THF (20 mL) was added dropwise to the reaction and the reaction was allowed to gradually warm at room temperature. The resultant reaction was stirred overnight. The reaction mixture was diluted with ethyl acetate (250 mL). The organic layers were combined, washed with saturated aqueous NaHCO3 (2×150 mL), H2O (1×50 mL), and brine (1×50 mL). The organic layers were dried over MgSO4 and concentrated in vacuo. The compound was triturated in ether to give of 2-phenylamino-6-trifluoromethyl-nicotinic acid (6.19 g, 98.9%) as a light brown solid. The material was not further purified.

1. customto give a dark red solution
2. temperatureto gradually warm at room temperature
3. customThe resultant reaction
4. stirringwas stirred overnight
5. washwashed with saturated aqueous NaHCO3 (2×150 mL), H2O (1×50 mL), and brine (1×50 mL)
6. dry with materialThe organic layers were dried over MgSO4
7. concentrationconcentrated in vacuo
8. customThe compound was triturated in ether

ORD record

ord-b6bb97267fce47bb97c4141438f14469

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501732B2