Dibromodifluoromethane → 4-[5-(2,2-Difluoro-vinyl)-thiazol-2-yl]-piperazine-1-carboxylic acid tert-butyl ester

To a solution of 6.73 mmol triphenylphosphine in 13 ml N,N-dimethylformamide was added 6.73 mmol dibromodifluoromethane and the mixture was stirred at room temperature for 1 h. 3.36 mmol 4-(5-formyl-thiazol-2-yl)-piperazine-1-carboxylic acid tert-butyl ester was added and the mixture was then cooled to 0° C. 6.73 mmol zinc dust was added in small portions and stirring continued for 10 min at 0° C. The mixture was then allowed to warm to room temperature and stirring continued for a further 2 h. The reaction mixture was then filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography (SiO2, ethyl acetate/heptane) to afford the title compound as a white crystalline solid (yield 19%). MS (m/e): 332.3 (M+H+, 10%), 276.0 ([M+2H−tBu]+, 100%).

1. temperaturethe mixture was then cooled to 0° C
2. stirringstirring
3. waitcontinued for 10 min at 0° C
4. temperatureto warm to room temperature
5. stirringstirring
6. waitcontinued for a further 2 h
7. filtrationThe reaction mixture was then filtered
8. concentrationthe filtrate was concentrated in vacuo
9. customThe residue was purified by chromatography (SiO2, ethyl acetate/heptane)

ORD-Eintrag

ord-893b7398074045f48b844b52356d1857

Quelldatensatz

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07220744B2