h) Preparation of N-methyl-N-(3-[((N-tert-butoxycarbonyl-N-methylamino)acetyloxy)methyl]pyridin-2-yl)carbamic acid (1-chloroethyl) ester: 2-methylamino-3-pyridinemethanol (22 g, 0.159 mol) and diisopropylamine (36.1 mL, 0.207 mol, 1.3 eq.) were dissolved in methylene chloride (1 L) and cooled to about -13°C in an ethanol-ice bath. 1-Chloroethyl chloroformate (17.5 mL, 0.161 mol, 1.01 eq.) was slowly added dropwise over 1 h. Stirring of the reaction mixture was continued for 1 h after completion of the dropwise addition. Subsequently 2-((tert-butoxycarbonyl)(methyl)amino)acetic acid (39.2 g, 0.207 mol, 1.3 eq.) and WSC (39.7 g, 0.207 mol, 1.3 eq.) were added in one batch over 10 min. After addition of DMAP (5.8 g, 0.047 mol, 0.3 eq.), the reaction mixture was stirred at -7 °C for 2 hours. Upon completion of the reaction, the mixture was warmed to 25 °C and concentrated and the residue was dissolved in diethyl ether (1 L). The ether solution was transferred to a partition funnel and washed sequentially with 0.1N HCl (500 mL x 3), water (500 mL), saturated aqueous NaHCO3 solution (500 mL) and saturated brine (500 mL x 2). The organic phase was dried over anhydrous MgSO4 and concentrated under reduced pressure to give the crude product (48.2 g, about 72.9% yield), which could be used in the subsequent reaction without further purification.1H-NMR (270 MHz, CDCl3): δ1.42 (9H, d, J=24.1 Hz), 1.57 (1.5H, br.s), 1.88 (1.5H, br.s) ), 2.94 (3H, s), 3.37 (3H, s), 4.00 (2H, d, J=21.1Hz), 5.18 (2H, d, J=13.5Hz), 6.58 (1H, q, J=5.45,11.0Hz), 7.30 (1H, s), 7.82 (1H, d, J=6.9Hz), 8.47 (1H, s); FAB-MS: m/z 416 (M+H)+.
