Sodium Hydroxide → 7-(Benzyloxy)-4-chloroquinoline

HRID 2277367Notes

Reaction equation

HRID 2277367 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](O)=[CH:14][CH:15]=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:22])=O.[OH-].[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([Cl:22])=[CH:14][CH:15]=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 178516454HCID 178516454, compound

Product 1

HCID 220306577-(Benzyloxy)-4-chloroquinolineYield 91.6%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a suspension of 7-(benzyloxy)quinolin-4-ol (72 g, 287 mmol) in toluene (134 mL) was added phosphoryl trichloride (44 g, 287 mmol, Tianjin FuChen Chem. Co. Ltd.). The suspension was heated to 120° C. for 1 hour. The reaction mixture was then cooled to 70° C. and diluted with EtOAc (600 mL). The resulted mixture was stirred for 30 minutes while cooling down to 15° C. using an ice bath. The mixture was neutralized with 3 M NaOH aqueous solution to pH 7˜8 while maintaining the temperature of the solution under 20° C. The aqueous layer was separated and extracted with EtOAc (200 mL). The combined organic layers were washed with brine (200 mL), dried over anhydrous Na2SO4 and concentrated in vacuo to give the title compound as a pale yellow solid (70.8 g, 91.6%).

Workup

  1. temperatureThe reaction mixture was then cooled to 70° C.
  2. temperaturewhile cooling down to 15° C.
  3. temperaturewhile maintaining the temperature of the solution under 20° C
  4. customThe aqueous layer was separated
  5. extractionextracted with EtOAc (200 mL)
  6. washThe combined organic layers were washed with brine (200 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ce151f8cae384170b0db7104781bcef6
Source dataset
uspto-grants-2015_09
Patent number
US09133162B2

Reaction notes

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