1-Bromo-3,4,5-trifluorobenzene → 6-(6-Bromo-2,3,4-trifluorophenyl)-3,3-dimethylpiperidin-2-one

Temperature

0 °C

To a stirred solution of 1-bromo-3,4,5-trifluorobenzene (313 mg, 1.48 mmol) in THF (3 mL) at −78° C. was added tert-butyllithium (1.74 mL of a 1.7 M solution in pentane, 2.96 mmol) dropwise. The reaction mixture was stirred for 1 h at −78° C., 3 h at 0° C., and then cooled back down to −78° C. A solution of benzyl (SS)-5-[(tert-butylsulfinyl)imino]-2,2-dimethylpentanoate (250 mg, 0.741 mmol, described in Intermediate 3) in toluene (5 mL) was added. The reaction mixture was stirred for 20 min at −78° C., 16 h at ambient temperature, and 1 h at reflux. The solvent was removed in vacuo and the crude solid dissolved in DMSO (5 mL). The crude product was purified by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. Lyophilization provided the title compound. MS: m/z=337 (M+1).

1. temperaturecooled back down to −78° C
2. stirringThe reaction mixture was stirred for 20 min at −78° C., 16 h at ambient temperature
3. temperature1 h at reflux
4. customThe solvent was removed in vacuo
5. dissolutionthe crude solid dissolved in DMSO (5 mL)
6. customThe crude product was purified by HPLC
7. washeluting with a gradient of H2O

ORD record

ord-d1876075443544b0a06d8d7f392c3c81

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07893079B2