Step 3. Synthesis of tert-butyl (6-(hydroxymethyl)pyridin-3-yl)carbamate. Lithium aluminum hydride (LAH) powder (36 g, 0.96 mol) was suspended in anhydrous tetrahydrofuran (THF, 1000 mL) under nitrogen protection and the mixture was cooled to 0 °C. To this suspension was slowly added a solution of methyl 5-((tert-butoxycarbonyl)amino)pyridine-2-carboxylate (150 g, 0.60 mol) in anhydrous THF (1000 mL). The reaction mixture was gradually warmed up to room temperature at 0 °C and stirred continuously for 12 hours. Completion of the reaction was monitored by thin layer chromatography (TLC, petroleum ether/ethyl acetate = 1:1). Upon completion of the reaction, the reaction was quenched by dropwise addition of THF-water (9:1, 400 mL) followed by addition of 15% aqueous NaOH (90 mL) and water (50 mL) at 90 °C. The mixture was stirred for 0.5 h at room temperature. The mixture was stirred at 0 °C for 0.5 h, then filtered through a Celite pad and the filter cake was washed with THF (4 x 1000 mL). The filtrate was concentrated under reduced pressure to give the crude product, which was purified by silica gel column chromatography with petroleum ether/ethyl acetate (2:1 to 1:2) as eluent. The grades containing the target product were collected and concentrated to afford tert-butyl (6-(hydroxymethyl)pyridin-3-yl)carbamate (450 g, 67% yield) as a white solid.1H NMR (400 MHz, DMSO-d6) δ 9.58-9.40 (m, 1H), 8.59-8.45 (m, 1H), 7.95-7.78 (m, 1H), 7.42-7.22 (m, 1H), 7.95-7.78 (m, 1H). 7.42-7.22 (m, 1H), 5.42-5.21 (m, 1H), 4.58-4.40 (m, 2H), 1.48 (s, 9H).
![N-[6-(hydroxymethyl)-3-pyridinyl]-carbamic acid 1,1-dimethylethyl ester](/CAS/GIF/323578-38-7.gif)