Ethyl orthoformate → Benzonitrile, 2-fluoro-4-(methylamino)- (9CI)

To a solution of 2-fluoro-4-aminobenzonitrile [Ind. Chim. Belg., 39, 490-500 (1974)] (3.8 g, 28 mmol) in anhydrous triethyl orthoformate (50 mL) was added trifluoroacetic acid (0.16 g, 1.4 mmol). The solution was heated to reflux 45 min, cooled and concentrated to give a yellow crystalline solid. To a solution of this solid in absolute ethanol (60 mL) at 0° C. was added sodium borohydride (3.2 g, 84 mmol). The resulting suspension was stirred at RT for 20 min, heated at reflux for 1 h, cooled and concentrated to give a colorless solid. This residue was partitioned between ether and water and the aqueous layer was extracted with ether. The organic phases were combined, washed with brine and dried (sodium sulfate). Concentration gave a white solid which was slurried in 35% ethyl acetate:hexane (200 mL) and filtered to give the title compound (3.7 g, 88%). mp 110-112° C.; 1H NMR (400 MHz, CDCl3) δ 7.35 (m, 1H), 6.4 (dd, 1H), 6.3 (dd, 1H), 2.9 (s, 3H).

1. temperatureThe solution was heated
2. temperatureto reflux 45 min
3. temperaturecooled
4. concentrationconcentrated
5. customto give a yellow crystalline solid
6. temperatureheated
7. temperatureat reflux for 1 h
8. temperaturecooled
9. concentrationconcentrated
10. customto give a colorless solid
11. customThis residue was partitioned between ether and water
12. extractionthe aqueous layer was extracted with ether
13. washwashed with brine
14. dry with materialdried (sodium sulfate)
15. concentrationConcentration
16. customgave a white solid which
17. filtrationhexane (200 mL) and filtered

ORD record

ord-520639924eda4d0588e00e970eb04577

Source dataset

uspto-grants-2000_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06117866