4-Toluenesulfonyl chloride → 2-(6-Bromo-2-quinolinyl)ethyl 4-methylbenzenesulfonate

HRID 860862Notes

Reaction equation

HRID 860862 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH2:12][CH2:13][OH:14])[CH:6]=[CH:5]2.C(N(CC)CC)C.[C:22]1([CH3:32])[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1.C([O-])(O)=O.[Na+]>C(OCC)(=O)C.ClCCl>[CH3:32][C:22]1[CH:27]=[CH:26][C:25]([S:28]([O:14][CH2:13][CH2:12][C:7]2[CH:6]=[CH:5][C:4]3[C:9](=[CH:10][CH:11]=[C:2]([Br:1])[CH:3]=3)[N:8]=2)(=[O:30])=[O:29])=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 671046912-(6-Bromo-2-quinolinyl)ethanol

Product 1

HCID 865922242-(6-Bromo-2-quinolinyl)ethyl 4-methylbenzenesulfonateYield 88.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 500 mL round bottom flask was charged with the product from Example 42B (7.65 g, 0.030 mole), 4-N,N-dimethylaminopyridine (0.36 g, 0.003 mole), dichloromethane (100 mL) and triethylamine (9.3 g, 0.092 mmol). p-Toluenesulfonyl chloride (11.5 g, 0.060 mole) was added in portions, and the solution was stirred at rt for 6 hours. The solution was stripped down to dryness, and the crude product was taken into ethyl acetate (150 mL) and 5% NaHCO3 aq. solution (150 mL). The upper organic was washed with water (150 mL), concentrated, azeotroped with ethyl acetate (250 mL×2) to a volume of ˜50 mL. The slurry was diluted with heptane (50 mL), stirred at room temperature overnight, and then at 5° C. for 8 hours. The precipitate was collected by filtration, rinsed with heptane (20 mL), dried at 50° C. under vacuum overnight to afford 10.80 g of the product as an off-white solid; mp 107–109° C.; MS (ESI): 406, 408 (M+H)+; 1H-NMR (CDCl3) δ 7.92 (1H, m), 7.91 (1H, m), 7.7 (2H, m), 7.58 (2H, m), 7.25 (1H, d, J=8.4 Hz), 7.09 (2H, m), 4.56 (2H, t, J=6.3 Hz), 3.27 (2H, t, J=6.3 Hz), 2.33 (3H, s); 13C-NMR (CDCl3) δ 157.2, 145.9, 144.1, 135.0, 132.5, 132.3, 130.3, 129.2, 129.2, 127.7, 127.4, 122.5, 119.6, 69.2, 38.0, 21.8.

Workup

  1. washThe upper organic was washed with water (150 mL)
  2. concentrationconcentrated
  3. customazeotroped with ethyl acetate (250 mL×2) to a volume of ˜50 mL
  4. additionThe slurry was diluted with heptane (50 mL)
  5. stirringstirred at room temperature overnight
  6. waitat 5° C. for 8 hours
  7. filtrationThe precipitate was collected by filtration
  8. washrinsed with heptane (20 mL)
  9. customdried at 50° C. under vacuum overnight

Sources & evidence

ORD record
ord-9a73bbf4d0c540fbac3d52fbccc23766
Source dataset
uspto-grants-2006_12
Patent number
US07153889B2

Reaction notes

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