Potassium Acetate → (2-Chloro-6-o-tolylquinolin-3-yl)methanol

HRID 69073Notes

Reaction equation

HRID 69073 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([Cl:12])[C:6]([CH2:13][OH:14])=[CH:5]2.[C:15]1([CH3:24])[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1B(O)O.C([O-])(=O)C.[K+]>CC#N.O>[Cl:12][C:7]1[C:6]([CH2:13][OH:14])=[CH:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[CH3:24])[CH:3]=2)[N:8]=1

Participants

6

Reactant 3

HCID 517044Potassium AcetateHCID 27332672-Methylphenyl boronic acidHCID 24276141(6-Bromo-2-chloroquinolin-3-yl)methanol

Product 1

HCID 86675781(2-Chloro-6-o-tolylquinolin-3-yl)methanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of (6-bromo-2-chloroquinolin-3-yl)methanol (19.8 g, 72.5 mmol, prepared as in example 2, step 2), o-tolylboronic acid (10.4 g, 76.1 mmol), potassium acetate (21.3 g, 217.4 mmol) and dichlorobis(4-(di-tert-butylphosphino)-N,N-dimethylaniline)palladium (II) (0.51 g, 0.72 mmol) in CH3CN (300 ml) and water (100 ml) was heated in to reflux. After 2 h, the reaction was allowed to cool to RT and the aqueous phase was discarded. The organics were washed with 2×50% brine/water, and then 2× brine. The organics were concentrated to ˜100 mL, at which point the precipitate was filtered off to afford a pale yellow solid of (2-chloro-6-o-tolylquinolin-3-yl)methanol. Step 2: (2-chloro-6-o-tolylquinolin-3-yl)methanol (13.9 g, 49.0 mmol) was treated with DCM (100 ml) and thionyl chloride (106 ml, 1456 mmol) at ambient temperature. After 15 min, the solution was concentrated and azeotroped with 2×100 mL toluene, to afford a yellow solid of 2-chloro-3-(chloromethyl)-6-o-tolylquinoline.

Workup

  1. temperaturewas heated in
  2. temperatureto reflux
  3. washThe organics were washed with 2×50% brine/water
  4. concentrationThe organics were concentrated to ˜100 mL, at which point the precipitate
  5. filtrationwas filtered off

Sources & evidence

ORD record
ord-1bb2a6b678f240db8a0295862efce482
Source dataset
uspto-grants-2014_09
Patent number
US08822485B2

Reaction notes

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