Triphenylphosphine → HCID 131730268, compound

Participants

Reaction Steps

Under a nitrogen atmosphere, tris(dibenzylideneacetone)dipalladium(0) (332 mg) and triphenylphosphine (299 mg) were added to tetrahydrofuran (40 mL), and the mixture was stirred at room temperature for 1 hr. Ethyl 6-bromo-1-((S)-1-(tert-butyldimethyl-silanyloxymethyl)-2-methylpropyl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate (10.0 g) obtained in Step 7 of Example 1/1-methyl-2-pyrrolidinone (80 mL) solution and a solution (26.2 g) of 29% 3-chloro-2-fluorobenzylzinc bromide in tetrahydrofuran were successively added dropwise at room temperature. After completion of the dropwise addition, the mixture was stirred at 65° C. for 3 hr, and the completion of the reaction was confirmed by HPLC. After cooling the reaction mixture, toluene (50 mL) and 12.5% aqueous ammonium chloride solution (100 mL) were added, sufficiently stirring, and the aqueous layer was discarded. The organic layer was washed successively with 25% aqueous ammonium chloride solution (50 mL), twice with 2% aqueous ethylenediamine solution (50 mL), and with 10% aqueous sodium chloride solution (50 mL). After washing, the solvent was evaporated under reduced pressure. Isopropanol (50 mL) was added to the concentrated residue to give a solution of ethyl 1-((S)-1-(tert-butyldimethyl-silanyloxymethyl)-2-methylpropyl)-6-(3-chloro-2-fluorobenzyl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate in isopropanol. This was directly used in the next step.

Provenance & Evidence