Diethyl Ether → HCID 12043677, compound

HRID 2186417Notes

Reaction equation

HRID 2186417 reaction equation
[CH:1]([Mg]Cl)([CH3:3])[CH3:2].C(OCC)C.[Br:11][C:12]1[CH:21]=[C:20]2[C:15]([C:16](=O)[CH2:17][C:18]([CH3:23])([CH3:22])[O:19]2)=[CH:14][CH:13]=1.CN1CCCN(C)C1=O>C1COCC1>[Br:11][C:12]1[CH:21]=[C:20]2[C:15]([C:16]([CH:1]([CH3:3])[CH3:2])=[CH:17][C:18]([CH3:23])([CH3:22])[O:19]2)=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 14755365HCID 14755365, compound2×HCID 178418918HCID 178418918, compound

Product 1

HCID 12043677HCID 12043677, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 2.0 M solution of isopropyl magnesium chloride in diethyl ether (15.5 mL, 31 mmol) was added slowly to a solution of 7-bromo-2,2-dimethyl-chroman-4-one (Compound 65, 1.58 g, 6.2 mmol) and 1,3-dimethyl-3,4,5,6-tetrahydro 2(1H) pyrimidone (DMPU) (7.5 mL, 30 mmol) in 30 mL THF at −30° C. The reaction mixture was warmed to room temperature and stirred for 15 hours. The reaction was then quenched with water (20 mL), saturated NH4Cl (aq) (15 mL) and 10% HCl (20 mL) at −78° C. The mixture was warmed to room temperature, was extracted with ethyl acetate (3×30 mL), the combined extracts were washed with water and brine, dried (MgSO4), filtered, and concentrated in vacuo. The residue was then refluxed in 40 mL methanol with p-toluenesulfonic acid (160 mg) for 20 hours. The reaction mixture was made basic by addition of solid K2CO3, the solvent was removed and the residue was dissolved in diethyl ether (50 mL). The ether solution was washed with water (2×50 mL) and brine (50 mL), dried (MgSO4), filtered, and concentrated in vacuo. The resulting crude product was purified by column chromatography on silica gel (hexane) to give the title compound as a clear oil: (650 mg, 37%).

Workup

  1. customThe reaction was then quenched with water (20 mL), saturated NH4Cl (aq) (15 mL) and 10% HCl (20 mL) at −78° C
  2. temperatureThe mixture was warmed to room temperature
  3. extractionwas extracted with ethyl acetate (3×30 mL)
  4. washthe combined extracts were washed with water and brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. temperatureThe residue was then refluxed in 40 mL methanol with p-toluenesulfonic acid (160 mg) for 20 hours
  9. additionThe reaction mixture was made basic by addition of solid K2CO3
  10. customthe solvent was removed
  11. dissolutionthe residue was dissolved in diethyl ether (50 mL)
  12. washThe ether solution was washed with water (2×50 mL) and brine (50 mL)
  13. dry with materialdried (MgSO4)
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customThe resulting crude product was purified by column chromatography on silica gel (hexane)

Sources & evidence

ORD record
ord-99d67028c51647f586a8318f04d5b3d3
Source dataset
uspto-grants-2002_06
Patent number
US06403638B1

Reaction notes

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