5-Bromo-2-iodopyridine → Rac-[2-(5-bromo-pyridin-2-yl)-1-(3,4-dichloro-phenyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 0.705 g (2.41 mmol) 5-bromo-2-iodopyridine in 4.8 ml dry tetrahydrofuran were added at 0° C. drop-wise 1.20 ml (2.41 mmol) of a 2M solution of isopropylmagnesium chloride in tetrahydrofuran. The mixture was stirred at 0° C. for 1.5 h and then 0.250 g (0.688 mmol) rac-[(3,4-Dichloro-phenyl)-(methoxy-methyl-carbamoyl)-methyl]-carbamic acid tert-butyl ester (Intermediate 9) were added. The ice bath was removed and stirring continued at ambient temperature for 2 h. The reaction was quenched by addition of 7 ml saturated aqueous ammonium chloride solution. The mixture was diluted with water and extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and evaporated. The crude product was purified by flash-chromatography over silica gel with a heptane/ethyl acetate gradient beginning with 5% ethyl acetate. The title compound was obtained al light yellow solid: MS (ISP): 459.1 and 461.1 (M+H)+, 403.0 and 405.1 ((M-isobutene)+H)+ (100%).

Provenance & Evidence