Reaction Steps
To a solution of N-((2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yloxy)-malonamic acid methyl ester (P-5; 108 mg, 0.34 mmol) in dry THF (3 mL) was added 60% NaH (14.4 mg, 0.36 mmol) giving gas evolution. To this mixture was added 3-(4-bromomethylphenyl)-1-(4-trifluoromethoxyphenyl)-1H-[1,2,4]triazole (P-7; 106 mg, 0.26 mmol), and the resulting mixture was heated to 50° C. for 21 h. The mixture was then allowed to cool to room temperature and diluted with EtOAc and washed with H2O. The aqueous fraction was extracted with EtOAc. The organic fractions were combined, washed with brine, dried with anhydrous Na2SO4 and evaporated at room temperature under vacuum. The resulting crude material was purified by silica gel chromatography (eluting with 100% Hexane going to 50% EtOAc in Hexane over 15 min and then going to 100% EtOAc over an additional 20 min). The title product (56 mg, 34%) was isolated as a colorless glass: 1H NMR (300 MHz, CDCl3) δ 8.58 (s, 1H), 8.17 (d, J=8.4 Hz, 2H), 7.90-7.70 (m, 2H), 7.41 (dd, J=9.9, 8.4 Hz, 4H), 5.42-5.09 (m, 2H), 4.76 (d, J=15.9 Hz, 1H), 3.83-3.05 (m, 18H), 1,41-1.20 (m, 3H); 13C NMR (151 MHz, CDCl3) δ 167.80, 148.87, 141.93, 137.72, 135.95, 130.20, 128.71, 127.19, 122.81, 121.66, 119.95, 105.05, 82.11, 81.97, 79.79, 76.81, 70.28, 70.04, 60.48, 59.63, 59.20, 58.37, 52.76, 41.66, 30.10, 18.58; ESIMS m/z 639 (M+H).
