Diethyl Ether → 3-(3-fluorophenyl)-2-(1-hydroxyethyl)-6-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

Participants

Reaction Steps

To a stirring suspension of 3-(3-fluorophenyl)-6-methyl-4-oxo-4H-pyrido[1,2-a]-pyrimidine-2-carbaldehyde (1.3567 g, 4.806 mmol) in THF (48.06 mL) was added methylmagnesium bromide 3 M in Et2O (2.403 mL, 7.210 mmol) dropwise at 0° C. and the mixture was allowed to warm to rt and stirred at rt. After 5 h, the reaction was quenched with satd aq NH4Cl (50 mL) and water (50 mL) and extracted with EtOAc (50 mL×2). The combined organic layers were washed with water (50 mL×1), brine (50 mL×1), dried over Na2SO4, filtered, and concd under reduced pressure to give a dark red syrup. The dark red syrup was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column using 0 to 50% gradient of EtOAc in hexane over 25 min, then 50% isocratic of EtOAc in hexane for 10 min, 50 to 100% gradient of EtOAc in hexane over 10 min, and then 100% isocratic of EtOAc for 10 min as eluent to give 3-(3-fluorophenyl)-2-(1-hydroxyethyl)-6-methyl-4H-pyrido[1,2-a]pyrimidin-4-one as a solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 7.66 (1 H, dd, J=8.8, 6.8 Hz), 7.41-7.52 (2 H, m), 7.12-7.24 (3 H, m), 6.88-6.96 (1 H, m), 4.98 (1 H, d, J=6.3 Hz), 4.42-4.51 (1 H, m), 2.89 (3 H, s), 1.26 (3 H, d, J=6.3 Hz); Mass Spectrum (ESI) m/e=298.9 (M+1).

Provenance & Evidence