4'-Bromoacetanilide → HCID 58523235, compound

Temperature

200 °C

A microwave vessel was charged with 4′-bromoacetoanilide (1.19 g, 5.56 mmol), 2,2,6,6-tetramethyl-3,5-heptanedione (0.23 mL, 1.1 mmol), copper(I) chloride (0.22 g, 2.2 mmol), cesium carbonate (5.42 g, 16.7 mmol), 4-fluoro-2-methylphenol (0.70 g, 5.6 mmol), and N-methyl-2-pyrrolidone (5 mL). The reaction mixture was heated at 200° C. in a microwave oven for 20 minutes. The reaction mixture then was cooled to ambient temperature and diluted with deionized water (20 mL). The dilution was extracted with ethyl acetate (20 mL) and the extract combined with saturated sodium bicarbonate (aq., 100 mL). The mixture was washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was diluted with concentrated hydrochloric acid (15 mL) and the dilution was heated at 100° C. for 2 hours. The reaction mixture was cooled to ambient temperature and diluted with 4N sodium hydroxide until basic. The dilution was extracted with methylene chloride (30 mL) and the extract was washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated. Product was purified from the residue by reverse phase HPLC to give 4-(4-fluoro-2-methylphenoxy)aniline (0.33 g, 1.5 mmol, 27% yield) as off-white solid. MS (EI) for C13H12FNO. found 218.1 (MH+).

1. temperatureThe reaction mixture then was cooled to ambient temperature
2. extractionThe dilution was extracted with ethyl acetate (20 mL)
3. washThe mixture was washed with brine (30 mL)
4. dry with materialdried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. additionThe residue was diluted with concentrated hydrochloric acid (15 mL)
8. temperaturethe dilution was heated at 100° C. for 2 hours
9. temperatureThe reaction mixture was cooled to ambient temperature
10. additiondiluted with 4N sodium hydroxide until basic
11. extractionThe dilution was extracted with methylene chloride (30 mL)
12. washthe extract was washed with brine (30 mL)
13. dry with materialdried over anhydrous sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated
16. customProduct was purified from the residue by reverse phase HPLC

ORD record

ord-7ff19d4b49214e01a9c201d6c57c538a

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08791102B2