Ammonium Hydroxide → 1-(2-Amino-5-chlorophenyl)-2,2,2-trifluoroethanone

Temperature

0 °C

To a solution of N-(4-chlorophenyl)-2,2-dimethylpropanamide (6.7 g, 30 mmol) in anhydrous THF (100 mL) under nitrogen at 0° C. was added a solution of n-BuLi (2.5M, 30 mL, 70 mmol) in hexane in a dropwise fashion. After addition, the solution was kept stirring at 0° C. for 40 minutes and treated with a solution of 1-(trifluoroacetyl)imidazole (9 mL, 78 mmol) in anhydrous THF (10 mL). The reaction mixture was warmed to ambient temperature and kept for 18 hours. To the reaction solution was added a saturated aqueous ammonium chloride solution (50 mL) followed by addition of ethyl acetate (100 mL). The organic layer was separated and the solvent was removed in vacuo. The residue obtained was suspended in 3N aqueous hydrochloride solution (50 mL) and heated at reflux overnight. The reaction solution was cooled to room temperature and treated with a cold ammonium hydroxide solution to a pH above 8. The aqueous mixture was extracted with ethyl acetate (3×50 mL) and the organic layers were washed with brine and dried (MgSO4). After removal of solvent, the residue was purified by a flash chromatography (silica gel, hexane:ethylacetate/4:1) to afford the title compound as a yellow solid (1 g, 15%): mp 93-94° C.; 1H-NMR (CDCl3) δ7.70 (m, 1H), 7.33 (dd, 1H, J=9.0, 2.3 Hz), 6.70 (d, 1H, J=9.1 Hz), 6.45 (bs, 2H); MS (ESI) m/z 222(M−H, 100%), 224(M−H, 33%).

1. additionAfter addition
2. temperatureThe reaction mixture was warmed to ambient temperature
3. waitkept for 18 hours
4. customThe organic layer was separated
5. customthe solvent was removed in vacuo
6. customThe residue obtained
7. temperatureheated
8. temperatureat reflux overnight
9. temperatureThe reaction solution was cooled to room temperature
10. extractionThe aqueous mixture was extracted with ethyl acetate (3×50 mL)
11. washthe organic layers were washed with brine
12. dry with materialdried (MgSO4)
13. customAfter removal of solvent
14. customthe residue was purified by a flash chromatography (silica gel, hexane:ethylacetate/4:1)

ORD record

ord-bcc0fa6c08b34e6b8e844774b986bc9b

Source dataset

uspto-grants-2003_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06509334B1