Chlorotrimethylsilane → 6-(2,5-Dimethyl-pyrrol-1-yl)-3',4',5',6'-tetrahydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl ester

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Reaction Conditions

Reaction Steps

284 mg (4.34 mmol) of electrolytic zinc is put into suspension under an argon atmosphere, to which 0.033 ml of 1-2 dibromoethane and 1 ml of tetrahydrofuran are added. After stirring for 3 minutes at 60° C. the reaction medium is left to return to ambient temperature. 0.047 ml of trimethylsilyl chloride is added and stirring is carried out for 30 minutes at ambient temperature. 1 g (3.2 mmol) of 2 solubilized beforehand in 2 ml of tetrahydrofuran is added. This reaction mixture is stirred for 45 minutes at ambient temperature and it is added to a solution containing 30 mg (0.032 mmol) of tris(dibenzylideneacetone) dipalladium marketed by Aldrich and 30 mg (0.13 mmol) of tris(2-furyl)phosphine marketed by LANCASTER. Then 1 g (4 mmol) of 3 solubilized beforehand in 10 ml of tetrahydrofuran is added. The reaction mixture is left under magnetic stirring at 60° C. for 2 hours, then left to return to ambient temperature, filtered on clarcel and extracted between ethyl acetate and a saturated aqueous solution of sodium bicarbonate. After extracting the aqueous phase twice with ethyl acetate, the organic phases are combined and dried over magnesium sulphate. The ethyl acetate is evaporated off under reduced pressure (2 kPa) and the crude residue is purified by chromatography on silicagel eluting with a heptane/ethyl acetate mixture 4:1. 350 mg (yield=30%) of expected product is recovered in the form of a yellow oil.

Provenance & Evidence