反应详情

A solution of the compound obtained in step 2 above (1.5 g, 4.7 mmol) in dry tetrahydrofuran (THF; 10 mL) was treated with 3-hydroxybenzaldehyde (0.74 g, 6.06 mmol) and triphenylphosphine (1.59 g, 6.06 mmol). This solution was stirred at room temperature then treated with diethyl azodicarboxylate (0.96 mL, 6.06 mmol) in dry THF (5 mL). After 1 hr, TLC indicated some remaining 2-[3-(4-tert-butoxycarbonyl-1-piperazinyl)-2-pyrazinyloxy]ethanol. The reaction was heated at reflux under nitrogen for 5 h, then left to cool to room temperature overnight. TLC again showed unreacted starter. The mixture was treated with further triphenylphosphine (0.80 g, 3.03 mmol), diethyl azodicarboxylate (0.5 mL, 3.03 mmol) and 3-hydroxybenzaldehyde (0.40 g, 3.03 mmol), then stirred at RT for a further 3 hrs (reaction complete by TLC). The volatiles were removed in vacuo and the residue was purified by flash column on silica gel, eluting with petroleum ether/ethyl acetate (2:1). This furnished 0.33 g (16%) of the title product as a colourless oil. 1H NMR (CDCl3) δ 1.5 (s, 9H); 3.5 (bs, 8H), 4.45 (m, 2H); 4.75 (m, 2H); 7.2 (d, 1H); 7.45 (s, 1H); 7.5 (m, 2H); 7.6 (s, 1H); 7.75 (s, 1H).

1. temperatureThe reaction was heated
2. temperatureat reflux under nitrogen for 5 h
3. waitleft
4. temperatureto cool to room temperature overnight
5. stirringstirred at RT for a further 3 hrs
6. custom(reaction complete by TLC)
7. customThe volatiles were removed in vacuo
8. customthe residue was purified by flash column on silica gel
9. washeluting with petroleum ether/ethyl acetate (2:1)