5-(4-Methoxyphenyl)-3,6-dimethyl-3,4-dihydropyridin-2(1H)-one → HCID 19908330, compound

HRID 1534805Notes

Reaction equation

HRID 1534805 reaction equation
[CH3:1][CH:2]1[CH2:7][C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)=[C:5]([CH3:16])[NH:4][C:3]1=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1.[OH-].[Na+].O>[CH3:16][CH:5]1[CH:6]([C:8]2[CH:9]=[CH:10][C:11]([O:14][CH3:15])=[CH:12][CH:13]=2)[CH2:7][CH:2]([CH3:1])[CH2:3][NH:4]1

Participants

6

Reactant 2

HCID 132689775-(4-Methoxyphenyl)-3,6-dimethyl-3,4-dihydropyridin-2(1H)-oneHCID 21226445Aluminium lithium hydride

Product 1

HCID 19908330HCID 19908330, compoundYield 38%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent3×HCID 14798Sodium HydroxideSolvent

Procedure

A solution of 6.95 g (30 mmol) of 3,6-dimethyl-5-(4-methoxyphenyl)-3,4-dihydro-2-pyridone in 70 ml of tetrahydrofuran was added dropwise under nitrogen to a suspension of 1.7 g (45 mmol) of lithium aluminium hydride in 50 ml of dry tetrahydrofuran. After the reaction mixture had been refluxed for 90 minutes, it was cooled and 1.7 ml of water in 10 ml of tetrahydrofuran, 3.4 ml of 2N sodium hydroxide and 3.4 ml of water were added dropwise successive while cooling with ice. After refluxing for a short period of time the resulting precipitate was filtered off and rinsed thoroughly with warm tetrahydrofuran; the filtrate was evaporated under reduced pressure. The resulting crude product (6.5 g) was dissolved, without further purification, in 75 ml of absolute ethanol. 0.5 g of platinum oxide were added to this solution and the mixture was hydrogenated at room temperature and atmospheric pressure for 30 minutes. After removing the catalyst by filtration the ethanol was evaporated under reduced pressure. The resulting crude product (6 g) was purified by means of flash chromatography over 100 g of silicagel (Merck, grain size 0.040-0.063 mm) using a mixture of ethyl acetate, methanol and concentrated ammonia (93:6.5:0.5) as an eluent, succeeded by flash chromatography over 100 g of silicagel (Merck, grain size 0.040-0.063 mm) using a mixture of dichloromethane, methanol and concentrated ammonia (93:6.5:0.5) as an eluent. After combining and evaporating the desired fractions, totally 2.5 g (38%) of 2,5-dimethyl-3-(4-methoxyphenyl)piperidine were obtained.

Workup

  1. temperatureAfter the reaction mixture had been refluxed for 90 minutes
  2. temperatureit was cooled
  3. temperaturewhile cooling with ice
  4. temperatureAfter refluxing for a short period of time the resulting precipitate
  5. filtrationwas filtered off
  6. washrinsed thoroughly with warm tetrahydrofuran
  7. customthe filtrate was evaporated under reduced pressure
  8. dissolutionThe resulting crude product (6.5 g) was dissolved, without further purification, in 75 ml of absolute ethanol
  9. addition0.5 g of platinum oxide were added to this solution
  10. customwas hydrogenated at room temperature
  11. customAfter removing the catalyst
  12. filtrationby filtration the ethanol
  13. customwas evaporated under reduced pressure
  14. customThe resulting crude product (6 g) was purified by means of flash chromatography over 100 g of silicagel (Merck, grain size 0.040-0.063 mm)
  15. additiona mixture of ethyl acetate, methanol and concentrated ammonia (93:6.5:0.5) as an eluent
  16. additiona mixture of dichloromethane, methanol and concentrated ammonia (93:6.5:0.5) as an eluent
  17. customevaporating the desired fractions

Sources & evidence

ORD record
ord-c1f6d662762e4d78a4daee9568b6aa68
Source dataset
uspto-grants-1992_02
Patent number
US05091393

Reaction notes

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