Synthesis of N- 2-Pyridylmethyl -2-aminoethanol

The compound was prepared by a slight modification of previously published procedures [24, 25]. Pyridine 2-carboxaldehyde (4.42 g, 0.04 mol) in methanol (10 mL) was added drop wise to ethanolamine (2.42 mL, 0.04 mol) in methanol (20 mL) at 0 °C. The yellow solution was brought to room temperature and stirred for 2 h. Sodium borohydride (3.60 g, 0.1 mol) was added in small portions at 0 °C and the solution was stirred for a further 2 h. Water (30 mL) was added and the reaction mixture was concentrated to about 30 mL in vacuo. The remaining solution was extracted with dichloromethane (3 x 20 mL) and the combined organic phases were dried over sodium sulfate and the solvent removed under vacuum to yield a yellow oil. (2.50 g, 40.58 %). 

11 Synthesis of Ethyl 4-hydroxy-3,5-bis(((2-hydroxyethyl) (pyridin-2-ylmethyl)amino)methyl)benzoate (COzEtHsLl) 

Ethyl 3,5-bis(bromomethyl)-4-hydroxybenzoate (0.50 g, 14 mmol) in dichloro-methane (4 mL) was added dropwise to N-(2-pyridylmethyl)-2-aminoethanol (0.43 g, 28 mmol) and triethylamine (0.80 g) in tetrahydrofurane (4 mL) at 0 °C. The resulting yellow solution was stirred for 48 h and monitored with TLC, filtered to remove the white precipitate of triethylamine hydrobromide and the solvent removed under vacuum. The resulting brown oil was purified by flash column chromatography (ethyl acetate/methanol, 8 2,12 stain, Rf = 0.44) to yield a yellow oil (0.50 g, 72.2 %). 

To a solution of 2-methoxy-N-(pyridin-2-ylmethyl)aminoethanol (0.925 g, 5.6 mmol) and triethylamine (1.25 g) in tetrahydrofuran (10 mL) was added dropwise a solution of 4-bromo-2,6-bis(bromomethyl)phenol (1 g, 2.7 mmol) in dichloromethane (10 mL) at 0 °C. The reaction mixture was stirred for 72 h and filtered to remove the precipitate of triethylamine hydrobromide. Removal of the solvent resulted in a yellow oil which was further purified by flash column chromatography (1 g crude ligand, length = 30 cm, diameter = 1.5 cm, ethyl acetate (until firsthand is eluted) then methanol/ethyl acetate 1 5, FeCla stain, Rf = 0.55 in ethyl acetate). The ligand was obtained as a yellow oil (930 mg, 63 %). 

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