Sodium Chloride → Iodide Ion

Participants

Reaction Conditions

Reaction Steps

To the heat gun dried flask under nitrogen was added 7-((4-methoxybenzyl)oxy)-2-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydro-1H-pyrido[1,2-a]pyrazine-1,8(2H)-dione (700 mg, 1.761 mmol) in N,N-dimethylacetamide (DMA) (10 mL) followed by (S)-4-tert-butyl 1-(4-methoxybenzyl) 2-(((Z)-(1-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)-2-(((5R,6R,7R)-3-(iodomethyl)-2-(((4-methoxybenzyl)oxy)carbonyl)-5-oxido-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl)amino)-2-oxoethylidene)amino)oxy)succinate (Example 1h) (1828 mg, 1.761 mmol) in N,N-dimethylacetamide (DMA) (10 mL). Mixture was heated at 40° C. for 3 h. Cooled and stored in fridge overnight. The mixture was cooled to −40° C. and N,N-dimethylformamide (DMF) (10 mL) was added followed by phosphorus tribromide (0.332 mL, 3.52 mmol) dropwise over 10 min. Stirred at −40° C. for 30 min. Poured into the cooled solution of 5% sodium chloride. The resulting solid was filtered and dried to give crude 1-(((6R,7R)-7-((Z)-2-((((S)-4-(tert-butoxy)-1-((4-methoxybenzyl)oxy)-1,4-dioxobutan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetamido)-2-(((4-methoxybenzyl)oxy)carbonyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methyl)-1-(2-(7-((4-methoxybenzyl)oxy)-1,8-dioxo-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-2(8H)-yl)ethyl)pyrrolidin-1-ium, Iodide (2.6 g, 1.832 mmol, 104% yield). LCMS: (M+H)+: 1420.8

Provenance & Evidence