4,4-Dimethyl-3,4-dihydroquinolin-2(1H)-one → 4,4-Dimethyl-1,2,3,4-tetrahydroquinoline

HRID 1515337Notes

Reaction equation

HRID 1515337 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][C:8]1([CH3:19])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[NH:11][C:10](=O)[CH2:9]1>O1CCCC1.N>[CH3:7][C:8]1([CH3:19])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[NH:11][CH2:10][CH2:9]1

Participants

5

Reactant 2

HCID 142099454,4-Dimethyl-3,4-dihydroquinolin-2(1H)-oneHCID 21226445Aluminium lithium hydride

Product 1

HCID 132194414,4-Dimethyl-1,2,3,4-tetrahydroquinoline

Reagents, catalysts & solvents 2

HCID 222AmmoniaSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of aniline (4.43 g) in chloroform (20 ml), a solution of 3,3-dimethylacryloyl chloride (2.65 ml) in chloroform (10 ml) was added dropwise and heated under reflux for 1.5 hours. After insoluble materials were filtered off and washed with chloroform, the filtrate was washed sequentially with 1M aqueous hydrochloric acid and saturated aqueous sodium bicarbonate. The filtrate was dried over anhydrous magnesium sulfate and then filtered to remove the desiccant, followed by distilling off the solvent under reduced pressure. The resulting residue was converted into a powder form by addition of n-hexane, and then collected by filtration to give 3-methyl-N-phenylbut-2-eneamide (4.11 g) as a colorless powder. 3-Methyl-N-phenylbut-2-eneamide thus obtained (2.06 g) was melted at 130° C., to which aluminum chloride powder (1.88 g) was then added and stirred at 130° C. for 0.5 hours. After the reaction temperature was reduced to 85° C., aluminum chloride powder (0.27 g) was added and stirred at 85° C. for 1 hour. After cooling at room temperature, the reaction mixture was poured into ice-cold water and extracted with diethyl ether, and the organic layer was washed with brine. The aqueous layer was extracted with chloroform, and the resulting organic layer was combined with the organic layer obtained earlier, dried over anhydrous magnesium sulfate and then filtered to remove the desiccant, followed by distilling off the solvent under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=9:1 to 1:1), and the solvent was distilled off under reduced pressure. The residue was converted into a powder form by addition of n-hexane, and then collected by filtration to give 4,4-dimethyl-3,4-dihydroquinolin-2(1H)-one (1.01 g) as a colorless powder. A suspension of lithium aluminum hydride (0.43 g) in tetrahydrofuran (5 ml) was heated under reflux, to which a solution of 4,4-dimethyl-3,4-dihydroquinolin-2(1H)-one thus obtained (1.01 g) in tetrahydrofuran (10 ml) was then added dropwise and heated under reflux for 3.5 hours. The reaction mixture was allowed to stand overnight at room temperature, diluted with 28% aqueous ammonia under ice cooling, and then filtered to remove insoluble materials. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=19:1 to 4:1) to give the titled compound, i.e., 4,4-dimethyl-1,2,3,4-tetrahydroquinoline (0.84 g) as a light-yellow oil.

Workup

  1. temperaturewas heated
  2. additionwas then added dropwise
  3. temperatureheated
  4. temperatureunder reflux for 3.5 hours
  5. filtrationfiltered
  6. customto remove insoluble materials
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe resulting residue was purified by silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=19:1 to 4:1)

Sources & evidence

ORD record
ord-bc08eb4faba94d0da64b1ccdb4574fab
Source dataset
uspto-grants-2012_07
Patent number
US08222417B2

Reaction notes

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