Isopropyl iodide → 1-Isopropyl-7-methyl-1,2,3,4-tetrahydro-quinoline

HRID 1765419Notes

Reaction equation

HRID 1765419 reaction equation
[CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][NH:9]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH:18](I)([CH3:20])[CH3:19]>CN(C)C=O>[CH:18]([N:9]1[C:10]2[C:5](=[CH:4][CH:3]=[C:2]([CH3:1])[CH:11]=2)[CH2:6][CH2:7][CH2:8]1)([CH3:20])[CH3:19]

Participants

5

Reactant 3

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 4586807-Methyl-1,2,3,4-tetrahydroquinoline

Product 1

HCID 222683251-Isopropyl-7-methyl-1,2,3,4-tetrahydro-quinolineYield 82.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a cooled solution of 7-methyl quinoline (5.00 g, 35 mmol) and nickel (II) chloride hexahydrate (1.40 g, 6 mmol) in methanol (130 mL) was added sodium borohydride (5.50 g, 140 mmol) portionwise. The reaction mixture was stirred at 0° C. for 1 hour and then at room temperature for 3 hours. Hydrochloric acid (2N, 200 mL) was added to the black residue and the mixture stirred at room temperature until disappearance of the black precipitate. The acidic solution was neutralized with concentrated ammonium hydroxide and extracted with ether. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, filtered and evaporated to give 5.28 g of 7-methyl-1,2,3,4-tetrahydro-quinoline (100%), used without further purification. A mixture of 7-methyl-1,2,3,4-tetrahydro-quinoline (1.20 g, 8.2 mmol), potassium carbonate (2.3 g, 16.4 mmol) and isopropyl iodide (3.3 mL, 32.8 mmol) in N,N-dimethylformamide (10 mL) was heated at 60° C. with stirring for 24 hours. The solution was cooled to room temperature and washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated to give 1.28 g (82%) of 1-isopropyl-7-methyl-1,2,3,4-tetrahydro-quinoline. To a solution of 1-isopropyl-7-methyl-1,2,3,4-tetrahydro-quinoline (1.04 g, 5.5 mmol) in dichloromethane was added tetrabutylammonium tribromide (2.65 g, 5.5 mmol) and the solution stirred at room temperature for 5 hours. The solution was washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was chromatographed and silica gel (ethyl acetate/hexane, 1:9) to give 1.00 g of 6-bromo-1-isopropyl-7-methyl-1,2,3,4-tetrahydro-quinoline (67%).

Workup

  1. customused without further purification
  2. temperatureThe solution was cooled to room temperature
  3. washwashed successively with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-c36a3a60ea064fa3a538af21cabacf75
Source dataset
uspto-grants-2007_06
Patent number
US07226940B2

Reaction notes

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