Iodoethane → HCID 58381973, compound

Participants

Reaction Conditions

Reaction Steps

2-Bromo-7-iodo-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (17.5 g, 28.4 mmol) in THF (200 mL) was cooled to about −75° C. then n-BuLi (1.6 M in hexanes, 19.5 mL, 31.2 mmol) was added keeping the temperature between about −70 and −75° C. The mixture was stirred for about 5 min at about −75° C. The mixture was treated with EtI (6.2 mL, 77 mmol) then the temperature of the mixture was raised to about 15° C. over about 5 to 10 min. The mixture was stirred at about 20° C. for about 30 min then saturated aqueous NH4Cl (10 mL) was added. The mixture was stirred for about 15 min at about 20° C. then concentrated under reduced pressure. The material was partitioned between Et2O (200 mL) and water (100 mL) the layers were separated and then the aqueous layer was extracted with Et2O (100 mL). The combined organic layers were washed with saturated aqueous NaCl (50 mL), dried over anhydrous MgSO4, filtered and concentrated in vacuo. The material was applied to a 120 g silica column and eluted with 9:1 heptane/EtOAc. The fractions largely free of impurities were collected. The impure fractions were combined and evaporated then a second 80 g silica column was run on this material with 9:1 heptane/EtOAc as an eluent to give a second lot of material largely free of impurities. The material from the two columns were combined then further purified by flash chromatography on a 220 g silica gel cartridge with a gradient of 0 to 10% EtOAc/heptane to give 2-bromo-7-ethyl-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (7.16 g, 49%): LC/MS (Table 2, Method g) Rt=2.0 min; MS m/z 518 (M+H)+.

Provenance & Evidence