Water → 2-Fluoro-6-hydroxybenzonitrile

Temperature

190 °C

151 g (1 mol) of 2-fluoro-6-methoxybenzonitrile and 346.5 g (3 mol) of pyridinium hydrochloride were introduced into a 2 l flask and then slowly heated to 190° C. under a protective gas atmosphere and then stirred at this temperature for 5 h. The mixture was cooled by slowly stirring to room temperature overnight. Then 1000 ml of water were added, and the mixture was heated to 80° C. After adding 1000 ml of methyl tert.-butyl ether, the phases were separated and the aqueous phase was back-extracted twice with 500 ml of methyl tert.-butyl ether. The combined methyl tert.-butyl ether phases were washed once with 800 ml of 10% strength aqueous sodium hydroxide solution and once with 400 ml of water. The two aqueous phases were combined, adjusted to pH 2 with concentrated hydrochloric acid and washed three times with 500 ml of methylene chloride. Then, the combined organic phases were washed once with 10% strength hydrochloric acid. The organic phase was dried over sodium sulfate. Finally, the solvent was distilled off in vacuo. Yield: 120 g (87% of theory) of the desired product of purity >99% according to GC. 1H NMR (in D6 dimethylsulfoxide): δ=6.85 ppm (m, 2H, arom. H), 7.55 ppm (q, 1H, arom. H), 11.7 ppm (s, 1H, OH).

1. temperatureThe mixture was cooled
2. stirringby slowly stirring to room temperature overnight
3. temperaturethe mixture was heated to 80° C
4. customthe phases were separated
5. extractionthe aqueous phase was back-extracted twice with 500 ml of methyl tert.-butyl ether
6. washThe combined methyl tert.-butyl ether phases were washed once with 800 ml of 10% strength aqueous sodium hydroxide solution and once with 400 ml of water
7. washwashed three times with 500 ml of methylene chloride
8. washThen, the combined organic phases were washed once with 10% strength hydrochloric acid
9. dry with materialThe organic phase was dried over sodium sulfate
10. distillationFinally, the solvent was distilled off in vacuo

ORD record

ord-52ecc36887844482846232574769f47a

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07544637B2