反应详情

温度

120 °C

A mixture of 3-hydroxy-1-methyl-1H-pyridin-4-one (7.60 g, 60.7 mmol) and K2CO3 (0.84 g, 6.07 mmol) in trifluoroacetaldehyde methyl hemiacetal (26 mL) was sealed in a parallel reactor and stirred for overnight at 120° C. The reaction mixture was evaporated to dryness, and the residue was purified by flash column chromatography on silica gel using a mixture of isopropyl alcohol and a conc. NH4OH solution (80/20, v/v) as eluant. Pure fractions were combined together and evaporated to give the title compound as a white solid (2.32 g, 17% yield). HPLC purity (peak area percent) of this compound is 99% at λ=254 nm. 1H NMR (400 MHz, DMSO-D6) δ (ppm): 7.59 (d, J=7.2 Hz, 1H), 6.20 (d, J=7.4 Hz, 1H), 5.80 (q, J=8.5 Hz, 1H) and 3.83 (s, 3H); MS-ESI (m/z): 223.7 [M+1]+, 206, 158. Other fractions were combined to give a second crop of the product (8.26 g, 61% yield). HPLC purity (peak area percent) of this compound is 98% at λ=254 nm. HPLC method: Column: Waters Symmetry C18; 5 μm, 3.9×150 mm; Mobile phase: A=the aqueous phase: 0.035% HClO4 pH 2.5; B=the organic phase: CH3CN; gradient: % B: 0 min—10%, 10 min—90%, 12 min—90%, 15 min—10%; flow rate: 1 mL/min; wavelength: 220, 254, 280 nm.

1. customwas sealed in a parallel reactor
2. customThe reaction mixture was evaporated to dryness
3. customthe residue was purified by flash column chromatography on silica gel using
4. additiona mixture of isopropyl alcohol
5. customevaporated