Methyl iodide → tert-Butyl 7-methoxy-3,4-dihydroquinoline-1(2H)-carboxylate

HRID 1172994Notes

Reaction equation

HRID 1172994 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([OH:18])[CH:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:21]I>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([O:18][CH3:21])[CH:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 53432598Tert-butyl 7-hydroxy-3,4-dihydroquinoline-1(2H)-carboxylate

Product 1

HCID 59556816tert-Butyl 7-methoxy-3,4-dihydroquinoline-1(2H)-carboxylateYield 41.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 7-hydroxy-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester (120 mg, 0.48 mmol) in N,N-dimethylformamide (6 ml) was added sodium hydride (23 mg, 0.57 mmol, 60% dispersion in oil) and the reaction mixture was stirred at room temperature for 10 min. The mixture was then cooled to 0° C. and methyl iodide (0.04 ml, 0.64 mmol) was added dropwise. After stirring for 16 h at room temperature, the mixture was quenched by addition of water (10 ml) and extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over sodium sulphate, and concentrated in vacuo. The residue was purified by chromatography on silica gel (eluant: heptane/ethyl acetate gradient) to yield the title compound as a colourless oil (52 mg, 41%); MS (ISP): 264.0 ([M+H]+), 208.1 ([M+H-Me2C═CH2]+).

Workup

  1. temperatureThe mixture was then cooled to 0° C.
  2. stirringAfter stirring for 16 h at room temperature
  3. customthe mixture was quenched by addition of water (10 ml)
  4. extractionextracted three times with ethyl acetate
  5. washThe combined organic phases were washed with saturated brine
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by chromatography on silica gel (eluant: heptane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-35cfcfd572924c8782983a31e0db083b
Source dataset
uspto-grants-2010_11
Patent number
US07834044B2

Reaction notes

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