Sodium Hydroxide → 2-Chloro-6-methoxyquinoline

HRID 860014Notes

Reaction equation

HRID 860014 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=O)[CH:7]=[CH:6]2.P(Cl)(Cl)([Cl:16])=O.[OH-].[Na+]>C1(C)C=CC=CC=1>[Cl:16][C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 2282682-Hydroxy-6-methoxyquinoline

Product 1

HCID 836472-Chloro-6-methoxyquinoline

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

A suspension of 6-methoxy-1H-quinolin-2-one of Step B (5.136 g, 29.2 mmol) in toluene (100 mL) is treated with phosphorous oxychloride 913.8 mL) and heated at 95° C. under nitrogen for 2 hours. The crude mixture is poured into ice water and basified with 50% aqueous sodium hydroxide. The solution is extracted with ethyl acetate, the extracts are dried over anhydrous magnesium sulfate and evaporated to dryness. The residue is pre-absorbed on silica gel Merck-60 and flash chromatographed using a gradient of ethyl acetate (10–20%) in hexane to provide the title compound (5.25 g) as a white crystalline solid, m.p. 105–107° C.

Workup

  1. extractionThe solution is extracted with ethyl acetate
  2. dry with materialthe extracts are dried over anhydrous magnesium sulfate
  3. customevaporated to dryness
  4. customThe residue is pre-absorbed on silica gel Merck-60 and flash
  5. customchromatographed

Sources & evidence

ORD record
ord-c5a88913d4d24e8bbb33a15d799a0f3e
Source dataset
uspto-grants-2006_12
Patent number
US07153849B2

Reaction notes

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