Acetic Acid → 3-Bromo-2-ethyl-4H-pyrido[1,2-a]pyrimidin-4-one

HRID 1715040Notes

Reaction equation

HRID 1715040 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[C:8]([CH2:12][C:13]([O:15]CC)=O)(=O)[CH2:9][CH3:10].CC(O)=O.[Br:22]Br>O>[Br:22][C:12]1[C:13](=[O:15])[N:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]2=[N:1][C:8]=1[CH2:9][CH3:10]

Participants

6

Reactant 4

HCID 176Acetic Acid2×HCID 104392-AminopyridineHCID 24408BromineHCID 78656Ethyl 3-oxovalerate

Product 1

HCID 587969403-Bromo-2-ethyl-4H-pyrido[1,2-a]pyrimidin-4-oneYield 89.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of aminopyridine (32.6 g, 347 mmol), ethyl propionylacetate (50.0 g, 347 mmol) and AcOH (250 ml) were heated at reflux overnight. The solution was cooled to room temperature and was added additional 250 ml of acetic acid. The reaction was cooled in a water batch. The resulting solution was treated with 17.8 ml of bromine drop-wise over approximately 10 min. After stirring at room temperature for 2 hours. The precipitate was filtered. The solid was washed with ether two times and 40% ethyl acetate-hexanes once and dried in vacuum to give 31.5 g K2 as the first crop. The filtrate was concentrated to a small volume and the precipitate was filtered. The solid was washed with ether two times and 40% ethyl acetate-hexanes once and dried in vacuum to give 47.1 g of K2 as the second crop. Combined yield: 89.9% over two steps.

Workup

  1. temperatureat reflux overnight
  2. filtrationThe precipitate was filtered
  3. washThe solid was washed with ether two times and 40% ethyl acetate-hexanes once
  4. customdried in vacuum
  5. customto give 31.5 g K2 as the first crop
  6. concentrationThe filtrate was concentrated to a small volume
  7. filtrationthe precipitate was filtered
  8. washThe solid was washed with ether two times and 40% ethyl acetate-hexanes once
  9. customdried in vacuum
  10. customto give 47.1 g of K2 as the second crop

Sources & evidence

ORD record
ord-0e740ef1f160494cb7cd796c19415a18
Source dataset
uspto-grants-2010_09
Patent number
US07799795B2

Reaction notes

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