Hydrochloric Acid → 2-Chloro-5-fluoro-4-methoxyaniline

Temperature

55 °C

1-Chloro-4-fluoro-5-methoxy-2-nitro-benzene (16.3 g, 79.3 mmol) and Sn granules (29.1 g, 246 mmol) were suspended in water (200 mL). Concentrated HCl (79 mL, 952 mmol) was added dropwise over 20 min. The resulting mixture was heated to 55° C. for 3 h. The solution was cooled to room temperature and carefully quenched with 1 N NaOH. The thick mixture was filtered through celite eluting the ethyl acetate to give a clear solution which was extracted with ethyl acetate. The ethyl acetate layers were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to give 26 g (80%) of 2-chloro-5-fluoro-4-methoxyaniline: Crude 1H NMR (400 MHz, CDCl3): δ 6.88 (d, J=8.3 Hz, 1H), 6.57 (d, J=12.2 Hz, 1H), 3.79 (s, 3H), 3.77 (br s, 2H). The crude material was pure enough to carry on to the next step.

1. temperatureThe solution was cooled to room temperature
2. customcarefully quenched with 1 N NaOH
3. filtrationThe thick mixture was filtered through celite
4. washeluting the ethyl acetate
5. customto give a clear solution which
6. extractionwas extracted with ethyl acetate
7. washThe ethyl acetate layers were washed with brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-be493efc37c44551aee5efabc7654a20

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07067658B2