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

HRID 405962Notes

Reaction equation

HRID 405962 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13](=[O:14])[N:12]3[C:15]([CH3:19])=[CH:16][CH:17]=[CH:18][C:11]3=[N:10][C:9]=2[CH:20]=[O:21])[CH:5]=[CH:6][CH:7]=1.[CH3:22][Mg]Br.CCOCC>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13](=[O:14])[N:12]3[C:15]([CH3:19])=[CH:16][CH:17]=[CH:18][C:11]3=[N:10][C:9]=2[CH:20]([OH:21])[CH3:22])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 866637753-(3-fluorophenyl)-6-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-2-carbaldehydeHCID 178418573HCID 178418573, compound

Product 1

HCID 668313383-(3-fluorophenyl)-2-(1-hydroxyethyl)-6-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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 (50 mL×1), brine (50 mL×1)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customconcd under reduced pressure to give a dark red syrup
  7. customThe dark red syrup was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column
  8. customover 25 min
  9. wait50% isocratic of EtOAc in hexane for 10 min
  10. wait50 to 100% gradient of EtOAc in hexane over 10 min

Sources & evidence

ORD record
ord-0308d2e4ed534558bb767c9f1022e59b
Source dataset
uspto-grants-2014_06
Patent number
US08754089B2

Reaction notes

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