2-(Methylamino)ethanol → 2-((2-(6-Bromo-3,4-dihydroquinolin-1(2H)-yl)ethyl)(methyl)amino)ethanol

HRID 1922495Notes

Reaction equation

HRID 1922495 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12](=O)[CH2:13]Cl)[CH2:7][CH2:6][CH2:5]2.C(=O)([O-])[O-].[K+].[K+].[CH3:22][NH:23][CH2:24][CH2:25][OH:26]>C(#N)C.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][CH2:13][N:23]([CH3:22])[CH2:24][CH2:25][OH:26])[CH2:7][CH2:6][CH2:5]2

Participants

6

Reactant 3

HCID 80162-(Methylamino)ethanolHCID 11430Potassium CarbonateHCID 573433941-(6-Bromo-3,4-dihydro-1(2H)-quinolinyl)-2-chloroethanone2×

Product 1

HCID 573433972-((2-(6-Bromo-3,4-dihydroquinolin-1(2H)-yl)ethyl)(methyl)amino)ethanolYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 6-bromo-1-(2-iodoethyl)-1,2,3,4-tetrahydroquinoline (compound 1, 0.475 g, 1.298 mmol) in acetonitrile (19 mL) and water (1 mL) in a 50 mL pressure vessel fitted with a stir-bar was treated with potassium carbonate (1.793 g, 12.98 mmol) and 2-(methylamino)ethanol (0.975 g, 12.98 mmol) and the sealed vessel stirred at 80° C. overnight. After 18 hours the mixture was partitioned between CH2Cl2 (100 mL) and water (20 mL) and transferred to a separatory funnel. The organic layer was separated and the aqueous layer (pH=12); extracted further with CH2Cl2. The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to a brown residue. Purification on silica gel eluting with 5% 2M NH3 in methanol/95% dichloromethane yielded a pale yellow oil, 2 (341 mg, 84%). 1H-NMR (DMSO-d6) δ 7.06 (dd, 1H, J=8.8, 2.5 Hz), 6.99 (d, 1H, J=2.4 Hz), 6.48 (d, 1H, J=8.8), 4.34 (t, 1H, J=5.3 Hz), 3.44 (q, 2H, J=6.2 Hz), 3.32-3.25 (m, 4H), 2.64 (t, 2H, J=6.2 Hz), 2.47-2.41 (m, 4H), 2.23 (s, 3H), 1.83-1.76 (m, 2H). MS (ESI+): 313/315 (MH+, 100).

Workup

  1. customAfter 18 hours the mixture was partitioned between CH2Cl2 (100 mL) and water (20 mL)
  2. customtransferred to a separatory funnel
  3. customThe organic layer was separated
  4. extractionextracted further with CH2Cl2
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to a brown residue
  9. customPurification on silica gel eluting with 5% 2M NH3 in methanol/95% dichloromethane

Sources & evidence

ORD record
ord-8ab59a9c098e460f98854b6944ac57aa
Source dataset
uspto-grants-2012_05
Patent number
US08173813B2

Reaction notes

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