4-Amino-3,5-difluorobenzoic acid

4-amino-3, 5-difluorobenzonitrile (354.3 mg, 2.3 mmol) was suspended in 1M aqueous sodium hydroxide (12 mL) and the resulting suspension was heated at 110 °C for 16 h. After cooling, the mixture was washed with ether. The aqueous phase was acidified to pH = 2 with 10percent KHS04/Na2S04 buffer and extracted with EtOAc (2X). The combined EtOAc extracts were washed with water, and then brine, dried over anhydrous sodium sulfate and concentrated in vacuo to provide 4-amino-3, 5-difluorobenzoic acid (335 mg, 84percent yield) as a yellow solid. 1H NMR (300 MHz, Chloroform-d) δ 7.66 - 7.58 (m, 2H).4-amino-3, 5-difluorobenzonitrile (354.3 mg, 2.3 mmol) was suspended in 1M aqueous sodium hydroxide (12 mL) and the resulting suspension was heated at 110 °C for 16 h. After cooling, the mixture was washed with ether. The aqueous phase was acidified to pH = 2 with 10percent KHS04/Na2S04 buffer and extracted with EtOAc (2X). The combined EtOAc extracts were washed with water, and then brine, dried over anhydrous sodium sulfate and concentrated in vacuo to provide 4-amino-3, 5-difluorobenzoic acid (335 mg, 84percent yield) as a yellow solid. 1H NMR (300 MHz, Chloroform-d) δ 7.66 - 7.58 (m, 2H).Step S2: 25 g of 2, 6-difluoro-4-cyanoaniline is dissolved in 800 mL of 1 M sodium hydroxide solution.After refluxing for 18 h, the reaction was completed by TLC thin layer chromatography and cooled to room temperature.Adjust the system to pH=8 with 1N hydrochloric acid, precipitate a large amount of solid, and filter by suction.The solid was dissolved in 500 mL of ethyl acetate and dried over anhydrous sodium sulfate (20 g).The product was concentrated to give a pale yellow solid (20.2 g).The yield was 71.4percent.[4- Amino-3, 5-difluorobenzoic acid (500 mg, 2.89 mmol) was dissolved in 20 mL of MeOH, to which 1.75 mL of concentrated sulfuric acid was added. The reaction was heated to reflux for 14 hours. After the reaction, the solvent was removed in vacuo and 20 mL of water was added, leading to the precipitation of the product, which was collected and dried on a funnel to provide the title product (417 mg, 77%) as a white solid, which was used in the next reaction without further purification. *H NMR (500 MHz, CDCh) d 7.58 - 7.46 (m, 2H), 4.14 (s, 2H), 3.87 (s, 3H).A mixture of

Molecular Weight:173.12
XLogP3:1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:1
Exact Mass:173.02883473
Monoisotopic Mass:173.02883473
Topological Polar Surface Area:63.3
Heavy Atom Count:12
Complexity:176
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes