[3-(1H-1,2,4-TRIAZOL-1-YLMETHYL)PHENYL]METHANOL synthesis

Yield:871825-54-6 22%

Reaction Conditions:

with sodium tetrahydroborate at 80; for 16 h;Solvent: polyethylene glycol;

Steps:

(3-((lH-l,2,4-TriazoI-l-yI)methyl)phenyI)methanol (TJA02011) C₁₀H₁₁N₃O MW 189.21. A 25 mL r.b. flask was loaded with TJA02008 (0.500 g, 2.36 mmol) and polyethylene glycol 400 (6.0 g). The mixture was heated to 80 ⁰C with stirring until a solution had formed. Sodium borahydride (0.261 g, 6.91 mmol) was added carefully resulting in evolution of gas. The reaction mixture was stirred vigorously at 80 ⁰C for 16 h. Extremely viscous glue formed that gradually dissolved in dichloromethane (50 mL) with heating (40 ⁰C). This solution was washed with IM HCl_(aq) (10 mL) and then carefully neutralised with sodium bicarbonate. Washed with distilled water (50 mL x 4) and brine (50 mL), separated and dried over MgSO₄. Solvent removed in vacuo to leave a viscous yellow oil. Flash chromatography (20 g column, meihodβ) eluted the title compound as a colourless viscous oil (0.101 g, 22 %), R/. 0.24 (ethyl acetate); ¹H NMR (270 MHz, CDCl₃) δ 2.53 (IH₅ bs, ArCH₂OH)₅ 4.66 (2η, s, ArCH₂OH), 5.30 (2H₃ s, ArCH₂N), 7.14-7.17 (IH₅ m, ArH)₅ 7.29-7.37 (2H, m, ArH)₅ 7.89 (IH, s, C₂H₂N₃) and 8.00 (IH₅ s, C₂H₂N₃); ¹³C NMR (67.9 MHz, CDCl₃) δ 53.6 (CH₂), 64.7 (CH₂), 126.5 (CH), 127.2 (CH), 129.3 (CH), 134.8 (C), 142.2 (C), 143.1 (CH) and 152.2 (CH); HPLC (70 % CH₃CN in H₂O) t_τ= 3.647 (100 %); LCMS (APCI), m/z 189.75 (M⁺ + H, 100 %).

References:

WO2007/68905,2007,A1 Location in patent:Page/Page column 134-135