Methyl iodide → HCID 56848037, compound

Participants

Reaction Steps

To a solution of N-{4-[1-(4-trifluoromethoxyphenyl)-1 H-[1 ,2,4]triazol-3-yl]-benzyl}O-((2S ,3R,4R,5S ,6S)-3 ,4 ,5-trimethoxy-6-methyl-tetrahydropyran-2-yl)-hydroxylamine. (3; 205 mg, 0.38 mmol) in tetrahydrofuran (THF; 10 mL) was added diisopropylethylamine (DIEA; 300 μL, 1.7 mmol) followed by methyl iodide (250 μL, 4.0 mmol). This solution was heated to reflux. After 1 h, due to apparent precipitation of quaternized DIEA, anhydrous potassium carbonate (K2CO3) was added to the mixture along with methyl iodide (200 μL, 3.2 mmol), and the suspension was allowed to stir at reflux an additional 21 h. The mixture was then cooled to room temperature, diluted with H2O and extracted with EtOAc (2×). 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 60% EtOAc in Hexane). The title product (131 mg, 63%) was isolated as a pale yellow solid: mp 93-100° C.; 1H NMR (400 MHz, CDCl3) δ 8.63 (d, J=4.1 Hz, 1H), 8.16 (d, J=8.3 Hz, 2H), 7.88-7.75 (m, 2H), 7.52 (t, J=10.7 Hz, 2H), 7.39 (t, J=9.5 Hz, 2H), 4.37 (d, J=13.2 Hz, 2H), 3.98-2.89 (m, 15H), 1.25 (dd, J=24.7, 6.2 Hz, 3H); ESIMS m/z 553 (M+H).

Provenance & Evidence