Chlorotrimethylsilane → 5-[2-Benzyloxy-4-(4-ethylpyridin-2-ylmethyl)-phenyl]-1,1-dioxo-2-(2-trimethylsilanyl-ethyl)-1,2,5-thiadiazolidin-3-one

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

In pressure vessels, zinc powder (2.145 g, 33 mmol) is dried by heating under vacuum, then cooled, placed under N2, and slurried in N,N-dimethylacetamide (4 mL). To the slurry is added 1,2-dibromoethane (220 μL, 2.55 mmol) and the mixture is heated until boiling. The mixture is allowed to cool, and TMSCl (325 mL, 2.55 mmol) is added, followed by stirring for 30 min. to produce a green solution. To the slurry of activated zinc is added 5-(2-benzyloxy-4-iodomethylphenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one (3.0 g, 5.37 mmol) in N,N-dimethylacetamide (5 mL) over 30 min. The organozinc solution is filtered and degassed with N2, then to it is added Pd2(dba)3 (250 mg, 0.275 mmol) and 2-(di-t-butylphosphino)biphenyl (330 mg, 1.1 mmol), followed by degassed 2-bromo-4-ethylpyridine (1.20 g, 6.44 mmol) in N,N-dimethylacetamide. The vessels are sealed and the reaction heated in the microwave in 4 batches, 120° C. for 20 min. The reaction is allowed to cool to ambient temperature, then filtered through Celite. The resulting solutions are combined and diluted with EtOAc (150 mL) and washed with water and brine, then dried over MgSO4. The solvent is removed under reduced pressure and the crude residue is purified via silica gel chromatography using a gradient of 0-75% EtOAc/hexanes to afford the title compound as a colorless oil: MS (M+H)+=616.

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