Diethyl Ether → (1-Ethyl-7-methoxy-2-oxo-1,2-dihydro-quinolin-3-yl)-acetic acid methyl ester

HRID 2301973Notes

Reaction equation

HRID 2301973 reaction equation
[CH3:1][O:2][C:3](=[O:18])[CH2:4][C:5]1[C:6](=[O:17])[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[C:10]([O:15][CH3:16])[CH:9]=2.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:29](I)[CH3:30].CCOCC>O1CCCC1>[CH3:1][O:2][C:3](=[O:18])[CH2:4][C:5]1[C:6](=[O:17])[N:7]([CH2:29][CH3:30])[C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[C:10]([O:15][CH3:16])[CH:9]=2

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 6340IodoethaneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 12071329(7-Methoxy-2-oxo-1,2-dihydro-quinolin-3-yl)-acetic acid methyl ester

Product 1

HCID 69978872(1-Ethyl-7-methoxy-2-oxo-1,2-dihydro-quinolin-3-yl)-acetic acid methyl esterYield 79.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A slurry of (7-methoxy-2-oxo-1,2-dihydro-quinolin-3-yl)-acetic acid methyl ester (5.0 g, 20 mmol) in tetrahydrofuran (40 mL) was treated with potassium bis(trimethylsilyl)amide (0.5 M in toluene, 41 mL, 21 mmol) at 25° C. and the mixture heated to reflux. After 1 h at reflux, ethyl iodide (16 mL, 200 mmol) was added. After an additional 3 h at reflux, the cooled mixture was quenched with 0.1N aqueous HCl (50 mL) and concentrated in vacuo. Water (200 mL) was added and the aqueous phase extracted with chloroform (3×200 mL). The extracts were dried (K2CO3) and concentrated in vacuo to give the crude product (5.3 g). Flash chromatography (225 g silica; 2:1, then 1:1 hexane-ether, then 100% ether) gave the title compound (4.4 g, 79% yield) as a white solid.

Workup

  1. temperaturethe mixture heated to reflux
  2. temperatureAfter 1 h at reflux
  3. temperatureAfter an additional 3 h at reflux
  4. customthe cooled mixture was quenched with 0.1N aqueous HCl (50 mL)
  5. concentrationconcentrated in vacuo
  6. additionWater (200 mL) was added
  7. extractionthe aqueous phase extracted with chloroform (3×200 mL)
  8. dry with materialThe extracts were dried (K2CO3)
  9. concentrationconcentrated in vacuo
  10. customto give the crude product (5.3 g)

Sources & evidence

ORD record
ord-4503143172e74f509e961d9f7b000960
Source dataset
uspto-grants-2002_08
Patent number
US06429214B1

Reaction notes

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