Diethyl Ether → HCID 66831350, compound

Temperature

9 °C

To a stirring suspension of 3-bromo-7-fluoro-4-oxo-4H-pyrido[1,2-a]pyrimidine-2-carbaldehyde (2.3555 g, 8.691 mmol) in THF (86.91 mL) was added methyl-magnesium bromide 3 M in Et2O (4.345 mL, 13.04 mmol) dropwise at 0° C. and the mixture was allowed to warm to 9° C. over 1.5 h. After 1.5 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 (100 mL×1), brine (100 mL×1), dried over Na2SO4, filtered, and concd under reduced pressure to give a red syrup. The red syrup was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column using 0 to 100% gradient of EtOAc in hexane over 25 min and 100% isocratic of EtOAc in hexane for 4 min as eluent to give 3-bromo-7-fluoro-2-(1-hydroxyethyl)-4H-pyrido[1,2-a]pyrimidin-4-one as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.92-8.97 (1 H, m), 8.14 (1 H, ddd, J=9.9, 7.1, 2.9 Hz), 7.83-7.90 (1 H, m), 5.26 (1 H, d, J=6.7 Hz), 5.09 (1 H, qd, J=6.5, 6.3 Hz), 1.38 (3 H, d, J=6.7 Hz); Mass Spectrum (ESI) m/e=286.9 [M+1 (79Br)] and 289.0 [M+1 (81Br)].

1. customthe reaction was quenched with satd aq NH4Cl (50 mL) and water (50 mL)
2. extractionextracted with EtOAc (50 mL×2)
3. washThe combined organic layers were washed with water (100 mL×1), brine (100 mL×1)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. customconcd under reduced pressure to give a red syrup
7. customThe red syrup was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column
8. customover 25 min

ORD record

ord-4f19238357a5411ebba221b7a71a0b9b

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08754089B2