Trifluoroacetic acid → HCID 22042623, compound

Temperature

-78 °C

To a solution of 1.03 g (3.23 mmol) of N-(4-bromo-2-methylphenyl)-N-methyl-benzenesulfonamide in 30 ml THF at −78° C. was added dropwise 3.9 ml (6.63 mmol) of a 1.7M solution of tert-BuLi in hexanes and the resultant mixture was stirred at −78° C. for 0.5 h. To this mixture was then added 0.66 ml (4.7 mmol) of 2,2,2-trifluoroacetophenone and the mixture stirred at −78° C. for an additional 0.5 h. The reaction was quenched by the addition of a saturated aqueous solution of ammonium chloride, allowed to warm to room temperature, and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered and the filtrate was concentrated. 253 mg (0.61 mmol) of this material and 3 ml of TFA was heated to 50° C. for 4 hours. After this time, excess TFA was removed in vacuo, water was added and the mixture was neutralized by the addition of a saturated aqueous solution of NaHCO3. The mixture was extracted with EtOAc and combined organic layers were washed with brine, dried over MgSO4, filtered and the filtrate was concentrated. The residue was purified by chromatography (silica, hexanes:EtOAc, 3:1) to give the title compound. 1H-NMR (CDCl3) δ 2.12 (s, 3H), 2.92 (s, 3H), 6.57 (d, J=8.5 Hz, 1H), 7.16 (s, 1H), 7.16 (brs, 1H), 7.37-7.41 (m, 3H), 7.54-7.56 (m, 2H). Mass Spectrum (CI+) m/e=296.1 (M+1).

1. customThe reaction was quenched by the addition of a saturated aqueous solution of ammonium chloride
2. temperatureto warm to room temperature
3. extractionextracted with EtOAc
4. washThe combined organic layers were washed with brine
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationthe filtrate was concentrated
8. customAfter this time, excess TFA was removed in vacuo, water
9. additionwas added
10. additionthe mixture was neutralized by the addition of a saturated aqueous solution of NaHCO3
11. extractionThe mixture was extracted with EtOAc
12. washwere washed with brine
13. dry with materialdried over MgSO4
14. filtrationfiltered
15. concentrationthe filtrate was concentrated
16. customThe residue was purified by chromatography (silica, hexanes:EtOAc, 3:1)

ORD record

ord-b05916d6e1c14d809738b3638b20e6e8

Source dataset

uspto-grants-2008_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07326812B2