N,N-Dimethylaniline → Methyl 2-(4-chloro-6-methyl-2-phenylpyrimidin-5-yl)pentanoate

HRID 1399626Notes

Reaction equation

HRID 1399626 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[NH:5][C:6](=O)[C:7]=1[CH:8]([CH2:13][CH2:14][CH3:15])[C:9]([O:11][CH3:12])=[O:10].P(Cl)(Cl)([Cl:25])=O.CN(C)C1C=CC=CC=1>C1(C)C=CC=CC=1>[Cl:25][C:6]1[C:7]([CH:8]([CH2:13][CH2:14][CH3:15])[C:9]([O:11][CH3:12])=[O:10])=[C:2]([CH3:1])[N:3]=[C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:5]=1

Participants

5

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 136346147Methyl 2-(4-methyl-6-oxo-2-phenyl-1,6-dihydropyrimidin-5-yl)pentanoate

Product 1

HCID 86665652Methyl 2-(4-chloro-6-methyl-2-phenylpyrimidin-5-yl)pentanoateYield 73%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a suspension of methyl 2-(4-methyl-6-oxo-2-phenyl-1,6-dihydropyrimidin-5-yl)pentanoate (0.900 g; 3 mmol) in dry toluene (6 mL) under a nitrogen atmosphere were carefully added phosphorus oxychloride (3 mL), dimethylaniline (0.3 mL) and the reaction mixture was heated to reflux for 3 h. The volatiles were removed under reduced pressure, the residue was cooled down in an ice-bath and quenched by adding crushed-ice and a saturated solution of sodium hydrogencarbonate until neutralization. The product was extracted with ethyl acetate, the combined organics were dried over magnesium sulphate, filtered and concentrated under reduced pressure. Purification by flash-chromatography on silica gel using a gradient of ethyl acetate (2-40%) in heptane furnished 0.701 g (73%) of the title compound as a colorless oil.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 3 h
  3. customThe volatiles were removed under reduced pressure
  4. temperaturethe residue was cooled down in an ice-bath
  5. customquenched
  6. additionby adding
  7. customcrushed-ice
  8. extractionThe product was extracted with ethyl acetate
  9. dry with materialthe combined organics were dried over magnesium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customPurification by flash-chromatography on silica gel using a gradient of ethyl acetate (2-40%) in heptane

Sources & evidence

ORD record
ord-d027b55712164ee0af1f30673af91960
Source dataset
uspto-grants-2014_12
Patent number
US08906906B2

Reaction notes

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