2-Chloroaniline → 5-Bromo-2-(2-chlorophenylamino)-3,4-difluorobenzoic acid

To a solution of 2-chloroaniline (20.13 g, 157.80 mmol) and 5-bromo-2,3,4-trifluorobenzoic acid (20.12 g, 78.90 mmol) in THF (120 mL) was added LiHMDS (236.7 mL, 1 M in THF, 236.7 mmol) dropwisely at −78° C. under nitrogen atmosphere. The mixture was allowed to slowly warm to room temperature and stirred at this temperature overnight. The reaction was quenched with water (100 mL) and acidified to pH 2-3 with 10% HCl (aq.). The mixture was extracted with ethyl acetate (100 mL×3). The combined organic extracts were washed with water (100 mL) and brine (100 mL) sequentially, dried over Na2SO4, filtered and concentrated in vacuo to afford the desired product (pale yellow solid, 25.63 g, 89.6% yield). 1H NMR (400 MHz, DMSO-d6): δ 14.10 (s, 1H), 9.30 (s, 1H), 8.03 (m, 1H), 7.47 (m, 1H), 7.23 (m, 1H), 7.04 (m, 2H).

1. customThe reaction was quenched with water (100 mL)
2. extractionThe mixture was extracted with ethyl acetate (100 mL×3)
3. washThe combined organic extracts were washed with water (100 mL) and brine (100 mL) sequentially
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo

ORD record

ord-4ebe9a1190854097a196e75d6d291f25

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09290468B2