Sodium Hydroxide → 1-(4-Chloro-3-fluorophenyl)-2-methylpropan-2-amine

Temperature

120 °C

A mixture of N-(1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl)acetamide (3.36 g, 13.80 mmol) and concentrated hydrochloric acid (60 mL) was heated at 120° C. for 16.5 h. The mixture was cooled to rt and poured into ice water and the resulting mixture was adjusted to pH>12 with NaOH and extracted with EtOAc (80 mL×5). The combined organic phases were washed with brine (100 mL×2), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo. The residue was dissolved in concentrated hydrochloric acid (60 mL) and the mixture was stirred at 120° C. for 20 h. The reaction mixture was cooled to rt and 100 mL of water was added. The resulting mixture was washed with EtOAc (50 mL×3). The aqueous phase was adjusted to pH>11 with NaOH and extracted with EtOAc (50 mL×3). The combined organic phases were washed with brine (80 mL×2), dried over anhydrous Na2SO4 (20 g) and concentrated in vacuo to give the tile compound as a yellow solid (0.484 g, 17.4%). The compound was characterized by the following spectroscopic data:

1. temperatureThe mixture was cooled to rt
2. extractionextracted with EtOAc (80 mL×5)
3. washThe combined organic phases were washed with brine (100 mL×2)
4. dry with materialdried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationThe filtrate was concentrated in vacuo
7. dissolutionThe residue was dissolved in concentrated hydrochloric acid (60 mL)
8. temperatureThe reaction mixture was cooled to rt
9. addition100 mL of water was added
10. washThe resulting mixture was washed with EtOAc (50 mL×3)
11. extractionextracted with EtOAc (50 mL×3)
12. washThe combined organic phases were washed with brine (80 mL×2)
13. dry with materialdried over anhydrous Na2SO4 (20 g)
14. concentrationconcentrated in vacuo

ORD record

ord-13307661c4144d0e97f0a9c4a365cfd1

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434695B2