Triphenylphosphine → 1-[7-(2-{[3-(1-Piperazinyl)-2-pyrazinyl]oxy}ethoxy)-1-benzofuran-2-yl]-1-ethanone, Hydrochloride

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Reaction Steps

DEAD (0.787 mL, 5.00 mmol) was added to a stirred solution of 2-[3-(4-tert-butoxycarbonyl-1-piperazinyl)-2-pyrazinyloxy]ethanol (1.50 g, 4.63 mmol; prepared in Example 52, Step 2), 2-acetyl-7-hydroxybenzofuran (0.88 g, 5.0 mmol) and PPh3 (1.31 g, 5.0 mmol) in THF (3 mL) under gentle heating. After being stirred for 30 min at room temperature, the reaction mixture was poured into water, extracted with EtOAc, dried (MgSO4) and concentrated. The residue was purified by column chromatography oil silica using toluene/EtOAc (7:3) as eluent. The pure fractions were combined and treated with CH2Cl2/TFA/H2O (50:45:5; 5 mL) for 30 min at room temperature. The mixture was poured into 0.5 M aqueous HCl and washed with EtOAc. The aqueous layer was alkalinized, by addition of NaOH, to pH 12 and extracted with EtOAc. The organic layer was dried (MgSO4), filtered and concentrated. The residue (0.250 g, 0.65 mmol) and pyridinium hydrochloride (0.075 g, 0.65 mmol) was dissolved in MeOH. The mixture was and concentrated and the residue was re-dissolved in EtOH and concentrated three more times to give 0.27 g (14%) of the title product. Pos-EI-MS shows M+ and 19 ions supporting the stated structure. HRMS m/z calcd for C20H22N4O4(M)+382.1641, found 382.1631.

Provenance & Evidence