Sodium Iodide → HCID 10152326, compound

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Reaction Steps

Combine a solution of 3,3-Bis-[4-(tert-butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-1,3-dihydro-indol-2-one (0.15 g, 0.250 mmol) in anhydrous tetrahydrofuran (6 ml), with 0.750 mL of 1N lithium bis(trimethlysilyl)amide in tetrahydrofuran. Stir the resulting mixture at room temperature for 0.25 h. In a separate flask, prepare a solution of 2,4-difluorobenzyl bromide (0.155 g, 0.750 mmol) and sodium iodide (0.011 g, 0.075 mmol) in anhydrous tetrahydrofuran. Stir at room temperature for 0.25 h then add this solution to the 3,3-Bis-[4-(tert-butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-1,3-dihydro-indol-2-one. Stir and heat the resulting mixture at 60° C. for 18 h. Cool to ambient temperature and dilute with 6 ml of methanol. Absorb the crude intermediate on 1 g of silica gel and evaporate the solvent under reduced pressure. Chromatograph this residue on a silica gel column eluting with 1:9 ethyl acetate/hexane. Combine the isolated intermediate, 3,3-Bis-[4-(tert-butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-1-(2,4-difluoro-benzyl)-1,3-dihydro-indol-2-one, with 4 ml of 1N CsF in methanol. Stir and heat at 60 C for 1 h then remove solvent in vacuuo. Dissolve the residue in 10 ml of water and extract with ethyl acetate (4×7 ml). Pass the ethyl acetate solution over anhydrous sodium sulfate and concentrate under vacuum. Triturate the residue with diethyl ether to obtain 0.097 g (78%) of the titled compound as granular crystals: LCMS (system 2) tR=4.13 min (100%), ESMS (M+1) m/z=499.56

Provenance & Evidence