Diethyl Ether → Methyl 2-(2-methylquinolin-8-yl)propanoate

HRID 338904Notes

Reaction equation

HRID 338904 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[C:7]([CH2:14][C:15]([O:17][CH3:18])=[O:16])[CH:8]=[CH:9][CH:10]=2)[N:5]=1.IC.[CH3:21]COCC>CS(C)=O.C1COCC1.[Cl-].[Na+].O>[CH3:3][C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[C:7]([CH:14]([CH3:21])[C:15]([O:17][CH3:18])=[O:16])[CH:8]=[CH:9][CH:10]=2)[N:5]=1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 70984092Methyl 2-(2-methylquinolin-8-yl)acetate

Product 1

HCID 70983048Methyl 2-(2-methylquinolin-8-yl)propanoateYield 100%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a mixture of NaH (0.58 g, 14.43 mmol) in DMSO (15 mL) at 20-35° C. was slowly added a solution of methyl 2-(2-methylquinolin-8-yl)acetate (1.35 g, 6.272 mmol) and iodomethane (1.08 ml, 17.25 mmol) in THF (5 mL). The reaction mixture was stirred at ambient temperature for 20 hours. Brine (20 mL) and ether (50 mL) were added. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure to give methyl 2-(2-methylquinolin-8-yl)propanoate (1.44 g, 100%) as an oil. The methyl 2-(2-methylquinolin-8-yl)propanoate (1.44 g, 6.28 mmol) was taken up in THF (10 mL) and 1 N lithium bis(trimethylsilyl)amide (12.56 mL, 12.56 mmol) in THF was added at 0° C. After addition, the reaction mixture was stirred at ambient temperature for 40 minutes. Iodomethane (0.78 mL, 12.56 mmol) was added dropwise and the reaction mixture was stirred at ambient temperature for 18 hours. Water (10 mL) and ether (50 mL) were added. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (8:1 hexane/ethyl acetate) to give methyl 2-methyl-2-(2-methylquinolin-8-yl)propanoate (0.67 g, 43.9%) as an oil.

Workup

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-69e1d7b43c204ac68e4909a94babce1d
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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