Methyl iodide → Ethyl 2-methoxy-2-(quinolin-5-yl)acetate

HRID 388261Notes

Reaction equation

HRID 388261 reaction equation
[OH:1][CH:2]([C:8]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:9]=1[CH:10]=[CH:11][CH:12]=[N:13]2)[C:3]([O:5][CH2:6][CH3:7])=[O:4].I[CH3:19].[H-].[Na+]>C1COCC1>[CH3:19][O:1][CH:2]([C:8]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:9]=1[CH:10]=[CH:11][CH:12]=[N:13]2)[C:3]([O:5][CH2:6][CH3:7])=[O:4]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydride2×HCID 59185877Ethyl 2-hydroxy-2-(quinolin-5-yl)acetate

Product 1

HCID 59185932Ethyl 2-methoxy-2-(quinolin-5-yl)acetateYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 2-hydroxy-2-(quinolin-5-yl)acetate (1.5 g, 6.5 mmol) in anhydrous THF in an oven-dried flask under argon was added iodomethane (1.2 mL, 19.2 mmol) and the mixture was cooled over an ice bath. NaH (60% in oil; 0.26 g, 6.5 mmol) was added and the mixture stirred for 1 hour over ice. After removing the ice bath, stirring was continued for an additional 3.25 hours, and more NaH (60%; 0.030 g, 0.75 mmol) was added. The mixture was stirred for 45 minutes then the reaction was quenched with brine and further diluted with water. The aqueous mixture was extracted with EtOAc and the combined organics were washed with water three times, brine once, dried over Na2SO4 and concentrated in vacuo. Purification by chromatography (50% EtOAc-hexanes) gave ethyl 2-methoxy-2-(quinolin-5-yl)acetate as a yellow oil (0.9 g, 57% yield).

Workup

  1. temperaturethe mixture was cooled over an ice bath
  2. customAfter removing the ice bath
  3. stirringstirring
  4. waitwas continued for an additional 3.25 hours
  5. stirringThe mixture was stirred for 45 minutes
  6. customthe reaction was quenched with brine
  7. additionfurther diluted with water
  8. extractionThe aqueous mixture was extracted with EtOAc
  9. washthe combined organics were washed with water three times, brine once
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated in vacuo
  12. customPurification by chromatography (50% EtOAc-hexanes)

Sources & evidence

ORD record
ord-d263e518edd74002a1df0563705a682c
Source dataset
uspto-grants-2013_02
Patent number
US08377930B2

Reaction notes

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