Dimethylformamide → 4-Bromo-2-fluoro-3-methoxybenzonitrile

Temperature

25 °C

Oxalyl chloride (20 mL) was added dropwise at 0° C. to a suspension of 4-bromo-2-fluoro-3-methoxybenzoic acid (8.30 g, 33.3 mmol) in 100 mL of DCM with 0.5 mL of DMF. The mixture was stirred at 25° C. for 2 hours and the clear solution was concentrated to dryness under reduced pressure. The residue dissolved in 60 mL of anhydrous acetonitrile was added to 600 mL of aqueous NH3.H2O at 0° C. and stirred for 2 hours then extracted with EtOAc twice. The combined EtOAc layer was washed with water and brine, dried over anhydrous Na2SO4 and concentrated. The residue (6.9 g) was dissolved in 60 mL of DMF and cooled to 0° C. with ice/water bath. Cyanuric chloride (7.70 g, 41.7 mmol) was added and stirred for 2 hours at 0° C. before poured to ice/water. The solid was collected by filtration and was washed with water, dissolved in DCM, dried over anhydrous Na2SO4 and concentrated to afford 4-bromo-2-fluoro-3-methoxybenzonitrile.

1. concentrationthe clear solution was concentrated to dryness under reduced pressure
2. dissolutionThe residue dissolved in 60 mL of anhydrous acetonitrile
3. additionwas added to 600 mL of aqueous NH3.H2O at 0° C.
4. stirringstirred for 2 hours
5. extractionthen extracted with EtOAc twice
6. washThe combined EtOAc layer was washed with water and brine
7. dry with materialdried over anhydrous Na2SO4
8. concentrationconcentrated
9. dissolutionThe residue (6.9 g) was dissolved in 60 mL of DMF
10. temperaturecooled to 0° C. with ice/water bath
11. stirringstirred for 2 hours at 0° C.
12. filtrationThe solid was collected by filtration
13. washwas washed with water
14. dissolutiondissolved in DCM
15. dry with materialdried over anhydrous Na2SO4
16. concentrationconcentrated

ORD record

ord-31d8e603b6524e94b14a7e37163392a6

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062070B2