Sodium Hydroxide → 4-[2-(2-Methyl-2-methyldisulfanyl-propylamino)-ethoxy]-2,6-bis-(hydroxymethyl)-pyridine

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Reaction Steps

To a suspension of 390 mg of 4-[2-amino-ethoxy]-2,6-bis-(hydroxymethyl)-pyridine (prepared after deprotection of the boc group of 4-(2-tert-butoxycarbonylamino-ethoxy)-2,6-bis-(hydroxymethyl)-pyridine described on page 101 of WO 07085930) in 2 mL of THF was added 270 μl of 2-(methyldithio)-isobutyraldehyde and 730 μL of titanium isopropoxide. After 20 min, a further 270 μl of 2-(methyldithio)-isobutyraldehyde and 730 μL of titanium isopropoxide were added and the mixture was stirred for 2 hours at room temperature. The mixture was then supplemented with 6 mL of ethanol, stirred for 20 min at room temperature and then supplemented with 124 mg of sodium cyanoborohydride. After stirring for 45 minutes, a further 124 mg of sodium cyanoborohydride were added and after stirring for 1 hour, the mixture was concentrated under reduced pressure, and diluted with EtOAc and water. The resulting precipitate was filtered off, and dissolved in aqueous 1M HCl solution. The aqueous phase obtained was brought to basic pH with aqueous 5M sodium hydroxide solution, extracted 3× with DCM and the combined organic phases were concentrated under reduced pressure. 322 mg of 4-[2-(2-methyl-2-methyldisulfanyl-propylamino)-ethoxy]-2,6-bis-(hydroxymethyl)-pyridine were obtained. 1H NMR (400 MHz, DMSO-d6): 1.26 (s, 6H); 1.81 (broad m, 1H); 2.39 (s, 3H); 2.67 (broad s, 2H); 2.94 (broad t, J=5.7 Hz, 2H); 4.11 (t, J=5.7 Hz, 2H); 4.45 (d, J=5.5 Hz, 4H); 5.32 (t, J=5.5 Hz, 2H); 6.85 (s, 2H). LC/MS (A): tr=0.24 min; [M+H]+: m/z 347.

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