2,4-Difluorobenzonitrile → 410545-57-2

Temperature

90 °C

2,4-difluorobenzonitrile (2.0 g, 14.38 mmol) and thiomethoxide (1.02 g, 14.38 mmol) were placed in an oven dried 100 mL round bottom flask fitted with a reflux condenser. Toluene (40 mL) was added and the reaction solution was put under an atmosphere of Argon. The reaction was heated to 90° C. over 48 hours. The crude reaction was cooled and concentrated in vacuo. The residue was taken up in methylene chloride and extracted with water. The organic phase was dried (MgSO4), filtered and concentrated to afford a white solid. The solid was dissolved in a minimal amount of methylene chloride and purified on an ISCO column (110 g silica) with a gradient of 100% to 80% hexanes/20% ethylacetate over 15 min at 45 ml/min, then 20% EtOAc/80% Hexanes for 5 min. The collected fractions were evaporated in vacuo to afford the desired material in a 7.5:1 ratio 4-fluoro-2-(methylthio)benzonitrile:2-fluoro-4-(methylthio)benzonitrile. The white solid was carried on to the next step without further purification.

1. customdried 100 mL round bottom flask
2. customfitted with a reflux condenser
3. additionToluene (40 mL) was added
4. customThe crude reaction
5. temperaturewas cooled
6. concentrationconcentrated in vacuo
7. extractionextracted with water
8. dry with materialThe organic phase was dried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated
11. customto afford a white solid
12. custompurified on an ISCO column (110 g silica) with a gradient of 100% to 80% hexanes/20% ethylacetate over 15 min at 45 ml/min
13. customThe collected fractions were evaporated in vacuo

ORD record

ord-42bcfa11b4444c9f93dea0558b930a59

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07279487B2