To a stirred solution of (2S,5R)-tert-butyl 5-(allyloxy(tert-butoxycarbonyl)amino)-2-(hydroxymethyl)-4-(methoxymethyl)-5,6-dihydropyridine-1(2H)-carboxylate (Intermediate 72, 8.82 g, 20.58 mmol) in 100 mL MeCN at 0° C., was added sodium periodate (19.37 g, 90.56 mmol). Then 12 mL of the stock oxidation solution was added. The suspension was then stirred at rt for 2d. An additional 16 mL the above stock solution was added and stirred for 2 more days. The mixture was diluted with 150 mL ethyl acetate, 50 mL 1M pH 7 buffer, and 50 mL 2M NaHSO3. The aqueous was extracted with 20 mL ethyl acetate. The ethyl acetate layer was then washed with brine. The aqueous layer was checked by LCMS and found containing desired carboxylic acid. The aqueous layer was then extracted with 50 mL ethyl acetate and washed with brine. The combined organic layers was dried over MgSO4, filtered and concentrated to afford a yellow dry film, (crude 7.11 g, 78%) which was used directly without further purification. To a stirred solution of (2S,5R)-5-(allyloxy(tert-butoxycarbonyl)amino)-1-(tert-butoxycarbonyl)-4-(methoxymethyl)-1,2,5,6-tetrahydropyridine-2-carboxylic acid (crude, 7.11 g, 16.07 mmol), ammonium chloride (1.719 g, 32.14 mmol), HATU (12.22 g, 32.14 mmol) in DMF (50.0 mL) at rt, was added DIPEA (8.31 g, 64.27 mmol). After stirring at rt for 1 hr, 100 mL EtOAc was added. The organic layer was washed with water, brine. The residue was purified by silica gel column (0-100% Hex/EA) to afford the desired product (3.07 g, 43.3%) as an off-white solid.
