Thioanisole → 3-[(6-Bromoquinolin-4-yl)oxy]-4-methylphenol

HRID 1675723Notes

Reaction equation

HRID 1675723 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[C:5]2Cl.C([O:20][C:21]1[CH:22]=[CH:23][C:24]([CH3:28])=[C:25]([OH:27])[CH:26]=1)C1C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].C1(SC)C=CC=CC=1>C(#N)C.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[C:5]2[O:27][C:25]1[CH:26]=[C:21]([OH:20])[CH:22]=[CH:23][C:24]=1[CH3:28]

Participants

7

Reactant 4

HCID 7520ThioanisoleHCID 11430Potassium CarbonateHCID 51395376-Bromo-4-chloroquinolineHCID 575815905-(Benzyloxy)-2-methylphenol

Product 1

HCID 578579503-[(6-Bromoquinolin-4-yl)oxy]-4-methylphenolYield 47%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
150 °C

Procedure

141 mg (0.58 mmol) of 6-bromo-4-chloroquinoline and 150 mg (0.7 mmol) 5-(benzyloxy)-2-methylphenol in 5 ml acetonitrile are mixed with 97 mg (0.7 mmol) of potassium carbonate and heated in the microwave oven to 150° C. for 3 h. The mixture is diluted with water and then extracted with ethyl acetate. The organic layers are washed with brine and dried over sodium sulfate. The solvent is evaporated and the resulting residue is dissolved in 5 ml TFA. 54 mg (0.44 mmol) thioanisole is added and the mixture is stirred over night. The solvent is evaporated, the resulting residue is dissolved in ethyl acetate and washed with sat. NaHCO3 and brine. The organic layers are dried over sodium sulfate, the solvent is evaporated and the resulting residue is purified by preparative HPLC. 90 mg (46%) of the desired product are obtained

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layers are washed with brine
  3. dry with materialdried over sodium sulfate
  4. customThe solvent is evaporated
  5. dissolutionthe resulting residue is dissolved in 5 ml TFA
  6. customThe solvent is evaporated
  7. dissolutionthe resulting residue is dissolved in ethyl acetate
  8. washwashed with sat. NaHCO3 and brine
  9. dry with materialThe organic layers are dried over sodium sulfate
  10. customthe solvent is evaporated
  11. customthe resulting residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-1cb94e1544e74301bd48e4c97bcb1179
Source dataset
uspto-grants-2011_08
Patent number
US08003787B2

Reaction notes

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