Trimethylsilyl cyanide → 2-(2-Bromo-4-chlorophenyl)-2-fluoroacetonitrile

Add 2-bromo-4-chloro-benzaldehyde (3.5 g, 16 mmol) in DCM (6 mL) to a flask that contains zinc iodide (8 mg). Stir the mixture at RT for 30 min. Cool the mixture to 0° C. with an ice-water bath. Add trimethylsilylcyanide (2.14 mL, 15.99 mmol) to the vigorously stirred mixture. Remove the cooling bath and stir at RT for 18 h. Add DCM (20 mL) and cool the mixture to 0° C. Add a solution of diethylaminosulfurtrifluoride (2.32 mL, 18 mmol) in DCM (8 mL) to the previous reaction mixture and stir the mixture overnight. Pour the reaction mixture into ice-water (50 mL) and separate the organic layer. Wash the organic layer with water, 0.5 N HCl, water, saturated NaHCO3, and water. Dry over magnesium sulfate. Remove the organic solvent to give the crude product. Purify by column chromatography (hexane/ethyl acetate, 10:1) to give the title compound (2.40 g, 74%). MS (GC) 249 [M]+.

1. temperatureCool the mixture to 0° C. with an ice-water bath
2. customRemove the cooling bath
3. stirringstir at RT for 18 h
4. temperatureAdd DCM (20 mL) and cool the mixture to 0° C
5. stirringstir the mixture overnight
6. customseparate the organic layer
7. washWash the organic layer with water, 0.5 N HCl, water, saturated NaHCO3, and water
8. dry with materialDry over magnesium sulfate
9. customRemove the organic solvent
10. customto give the crude product
11. customPurify by column chromatography (hexane/ethyl acetate, 10:1)

ORD record

ord-9c191017a28d4525bf67242fc65128c5

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08063035B2