反应详情

A solution of 2-[4-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-1-methyl-1H-1,2,3-triazol-5-yl]ethyl methanesulphonate (642 mg, 1.84 mmol) and azetidine (2.48 ml, 18.4 mmol) in THF (10 ml) was heated at reflux for 4 h and then concentrated under reduced pressure while dry loading onto silica. The mixture was purified by column chromatography on silica using 2% MeOH/CH2Cl2 containing 1% NH3 solution as eluent. After concentrating under reduced pressure, THF (3 ml), H2O (3ml) and AcOH (9 ml) were added and the mixture stirred at RT for 60 h. The solvents were removed under reduced pressure while azeotroping with toluene (2×25 ml). The residue was dissolved in CH2Cl2, dry loaded onto silica and purified by column chromatography on silica using 15% MeOH/CH2Cl2 containing 1% NH3 solution as eluent to yield the desired hydroxymethyltriazole (103 mg, 29%). 1H NMR (360 MHz, CDCl3) δ 4.65 (2H, s), 3.94 (3H, s), 3.25 (4H, t, J=7.2 Hz), 2.76-2.62 (4H, m), 2.11 (2H, quintet, 7.2 Hz). m/z (ES+) 196 (M+H+).

1. temperatureat reflux for 4 h
2. concentrationconcentrated under reduced pressure
3. customwhile dry loading onto silica
4. customThe mixture was purified by column chromatography on silica using 2% MeOH/CH2Cl2 containing 1% NH3 solution as eluent
5. concentrationAfter concentrating under reduced pressure, THF (3 ml), H2O (3ml) and AcOH (9 ml)
6. additionwere added
7. customThe solvents were removed under reduced pressure
8. customwhile azeotroping with toluene (2×25 ml)
9. dissolutionThe residue was dissolved in CH2Cl2
10. customdry loaded onto silica
11. custompurified by column chromatography on silica using 15% MeOH/CH2Cl2 containing 1% NH3 solution as eluent