Azetidine → [5-(2-(Azetidin-1-yl)ethyl)-1-methyl-1h-[1,2,3]triazol-4-yl]methanol

HRID 2183510Notes

Reaction equation

HRID 2183510 reaction equation
CS(O[CH2:6][CH2:7][C:8]1[N:12]([CH3:13])[N:11]=[N:10][C:9]=1[CH2:14][O:15][Si](C(C)(C)C)(C)C)(=O)=O.[NH:23]1[CH2:26][CH2:25][CH2:24]1>C1COCC1>[N:23]1([CH2:6][CH2:7][C:8]2[N:12]([CH3:13])[N:11]=[N:10][C:9]=2[CH2:14][OH:15])[CH2:26][CH2:25][CH2:24]1

Participants

4

Reactant 2

HCID 10422AzetidineHCID 879982852-[4-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)-1-methyl-1h-1,2,3-triazol-5-yl]ethyl methanesulphonate

Product 1

HCID 22473219[5-(2-(Azetidin-1-yl)ethyl)-1-methyl-1h-[1,2,3]triazol-4-yl]methanolYield 29%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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+).

Workup

  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

Sources & evidence

ORD record
ord-9f2836710fd6426a8fc57f24c34590d7
Source dataset
uspto-grants-2005_05
Patent number
US06900209B2

Reaction notes

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