Methylparaben → Methyl 4-[(quinolin-4-yl)methoxy]benzoate

HRID 900398Notes

Reaction equation

HRID 900398 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:13])[C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=1.Cl[CH2:15][C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[N:19]=[CH:18][CH:17]=1.[OH-].[Na+]>CN(C=O)C.CCCCCC>[CH3:3][O:4][C:5](=[O:13])[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]=[CH:18][CH:17]=2)=[CH:8][CH:7]=1

Participants

7

Reactant 4

HCID 7456MethylparabenHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 123557014-(Chloromethyl)quinoline

Product 1

HCID 53689041Methyl 4-[(quinolin-4-yl)methoxy]benzoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8058HexaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Sodium hydride (430 mg, 60%, 10.75 mmol) was placed in a flask with hexane and stirred under nitrogen. After 10 minutes the hexane was discarded and 10 ml dry DMF was added. After cooling to 0° C., 4-hydroxy-benzoic acid methyl ester Q-2 (1.67 g, 11 mmol) was added and the mixture stirred for 15 minutes. 4-Chloromethyl-quinoline Q-1 (1.8 g, 10.1 mmol) was dissolved in 3 mL of DMF and added dropwise to the reaction mixture. The temperature was raised to 130° C. and the mixture stirred for a half hour. After cooling to room temperature the reaction mixture was poured into 50 mL 1N sodium hydroxide solution and extracted three times with 20 mL dichloromethane. The combined organic layers were washed twice with water, dried over sodium sulfate and concentrated in vacuo. The crude product (2.5 g) was recrystallized from ethyl ether to give 4-(quinolin-4-ylmethoxy)-benzoic acid methyl ester (1.6 g, 5.45 mM) as a white solid.

Workup

  1. stirringthe mixture stirred for 15 minutes
  2. additionadded dropwise to the reaction mixture
  3. temperatureThe temperature was raised to 130° C.
  4. stirringthe mixture stirred for a half hour
  5. temperatureAfter cooling to room temperature the reaction mixture
  6. extractionextracted three times with 20 mL dichloromethane
  7. washThe combined organic layers were washed twice with water
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe crude product (2.5 g) was recrystallized from ethyl ether

Sources & evidence

ORD record
ord-ca819de813ae4c0681792a79e9720bd9
Source dataset
uspto-grants-2008_04
Patent number
US07358373B2

Reaction notes

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