Toluene → 2-Chloro-5,6,7,8-tetrahydroquinolin-5-one

HRID 875302Notes

Reaction equation

HRID 875302 reaction equation
[NH:1]1[C:10]2[CH2:9][CH2:8][CH2:7][C:6](=[O:11])[C:5]=2[CH:4]=[CH:3][C:2]1=O.P(Cl)(Cl)([Cl:15])=O.C1(C)C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(#N)C>[Cl:15][C:2]1[CH:3]=[CH:4][C:5]2[C:6](=[O:11])[CH2:7][CH2:8][CH2:9][C:10]=2[N:1]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 24813Phosphorus oxychlorideHCID 2674502-Hydroxy-7,8-dihydro-5(6H)-quinolinoneHCID 516892Sodium Bicarbonate

Product 1

HCID 5928392-Chloro-5,6,7,8-tetrahydroquinolin-5-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

Under nitrogen, 21.02 g (0.13 mol) of 7,8-dihydroquinoline-2,5(1H,6H)-dione were suspended in 100 ml of acetonitrile (anhydrous, <30 ppm H2O), and 135.28 ml (density 1.46 g/ml, 1.29 mol) of phosphorus oxychloride were added. The yellowish suspension was then heated to 75° C. and stirred at this temperature for 1.25 hours. The yellow clear solution was then cooled to room temperature, and 150 ml of toluene were added. The solution was then concentrated on a rotary evaporator to about 100 ml, and another 150 ml of toluene were added. The solution was then concentrated to dryness on a rotary evaporator. 300 ml of ethyl acetate were then added to the orange oil obtained. Subsequently, the solution was carefully (evolution of gas) added to 500 ml of saturated aqueous sodium bicarbonate solution and stirred for 15 min. The phases were separated and the aqueous phase was extracted with 200 ml of ethyl acetate. The combined organic phases were washed twice with 250 ml of water and once with 100 ml of saturated sodium chloride solution, dried over sodium sulphate, filtered and concentrated to dryness under reduced pressure. This gave 22.58 g (0.12 mmol, 96% of theory) of the target compound as a slightly yellowish solid.

Workup

  1. temperatureThe yellow clear solution was then cooled to room temperature
  2. concentrationThe solution was then concentrated on a rotary evaporator to about 100 ml
  3. additionanother 150 ml of toluene were added
  4. concentrationThe solution was then concentrated to dryness on a rotary evaporator
  5. addition300 ml of ethyl acetate were then added to the orange oil
  6. customobtained
  7. stirringstirred for 15 min
  8. customThe phases were separated
  9. extractionthe aqueous phase was extracted with 200 ml of ethyl acetate
  10. washThe combined organic phases were washed twice with 250 ml of water and once with 100 ml of saturated sodium chloride solution
  11. dry with materialdried over sodium sulphate
  12. filtrationfiltered
  13. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-b4b37ae4f9c34bec9de54ccd07b69d5f
Source dataset
uspto-grants-2015_03
Patent number
US08981104B2

Reaction notes

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