Methanol → 6-Aminomethyl-3-(tert-butoxycarbonylamino-methyl)-pyridine

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Reaction Steps

Add 3-(tert-butoxycarbonylamino-methyl)-6-cyano-pyridine (10.81 g, 46.4 mmol), KHSO4 (18.9 g, 16.2 mmol), 5% Pd/C (Degussa type E101, 4 g) to a mixture of methanol (250 mL) and water (20 mL) in a pressure vessel. Flush the vessel three times with hydrogen and charge with hydrogen to 50 psi. Stir at room temperature, recharging to 50 psi hydrogen as necessary, until no change in pressure is observed. Add an aqueous NaOH solution (6.11 g of NaOH in 20 mL of water) to the mixture and stir for 15 min. Filter the mixture through glass microfiber filter paper. Dilute the filtrate with water and DCM. Separate the layers, and extract the aqueous layer with DCM. Wash the combined organic extracts with water and brine. Dry the organic solution over Na2SO4, filter and concentrate in vacuo. Purify by chromatography on silica gel (600 g) eluting with DCM/(chloroform:methanol:concentrated NH4OH 80:18:2) (1:0 to 7:3 gradient) to obtain 6-aminomethyl-3-(tert-butoxycarbonylamino-methyl)-pyridine as a clear oil [3.4 g, 31%, MS (ES+) m/z: 238 (M+H)+] and the desired intermediate 3-(tert-butoxycarbonylamino-methyl)-6-hydroxymethyl-pyridine as colorless oil (5.6 g, 52%). MS (ES+) m/z: 239 (M+H)+.

Provenance & Evidence