Dimethylformamide → 3-Chloro-2-fluorophenylacetic acid

Temperature

75 °C

1-Bromomethyl-3-chloro-2-fluoro-benzene (10.00 g, 44.80 mmol) and KCN (5.80 g, 89.07 mmol) were mixed in DMF and the resulting reaction mixture was stirred at 75° C. for 2 days. The reaction mixture was cooled to room temperature, and water was added. The mixture was extracted with Et2O (3×300 mL). The combined organic phases were washed with H2O (2×200 mL) and brine (1×200 mL), then dried over MgSO4 and concentrated. The crude nitrile was taken up in water and KOH (5.00 g, 89.11 mmol) was added. The resulting mixture was refluxed for 14 hours. After cooling to room temperature, the reaction mixture was diluted with water and washed with Et2O (2×150 mL). The aqueous layer was acidified with concentrated HCl and was extracted with Et2O (3×300 mL). The combined organic phases were washed with H2O (2×200 mL) and brine (1×200 mL), then dried over MgSO4 and concentrated to afford the title acid.

1. customthe resulting reaction mixture
2. temperatureThe reaction mixture was cooled to room temperature
3. extractionThe mixture was extracted with Et2O (3×300 mL)
4. washThe combined organic phases were washed with H2O (2×200 mL) and brine (1×200 mL)
5. dry with materialdried over MgSO4
6. concentrationconcentrated
7. temperatureThe resulting mixture was refluxed for 14 hours
8. temperatureAfter cooling to room temperature
9. washwashed with Et2O (2×150 mL)
10. extractionwas extracted with Et2O (3×300 mL)
11. washThe combined organic phases were washed with H2O (2×200 mL) and brine (1×200 mL)
12. dry with materialdried over MgSO4
13. concentrationconcentrated

ORD record

ord-456c73bedac24f66a62015c9fe44fc2a

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08557853B2