Methyl iodide → 2-(5,7-Difluoro-quinolin-6-yl)-propionic acid methyl ester

HRID 1959734Notes

Reaction equation

HRID 1959734 reaction equation
[Li+].[CH3:2]C([N-]C(C)C)C.[CH3:9][O:10][C:11](=[O:25])[CH2:12][C:13]1[C:14]([F:24])=[C:15]2[C:20](=[CH:21][C:22]=1[F:23])[N:19]=[CH:18][CH:17]=[CH:16]2.CI>C1COCC1>[CH3:9][O:10][C:11](=[O:25])[CH:12]([C:13]1[C:14]([F:24])=[C:15]2[C:20](=[CH:21][C:22]=1[F:23])[N:19]=[CH:18][CH:17]=[CH:16]2)[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 58190558Methyl 2-(5,7-difluoroquinolin-6-yl)acetate

Product 1

HCID 581905742-(5,7-Difluoro-quinolin-6-yl)-propionic acid methyl esterYield 95.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of LDA (1.2 M in THF, 9.5 mL, 11.4 mmol) in dry THF (30 mL) at −78° C. was added a solution of (5,7-difluoroquinolin-6-yl)-acetic acid methyl ester (2.12 g, 9.5 mmol) in THF (20 mL) dropwise. After 30 min, MeI (0.9 mL, 14.2 mmol) was added dropwise, and the reaction mixture was allowed to rise to 0° C. naturally. After 1 h, the reaction was quenched by saturated aqueous NaHCO3 solution, and extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, concentrated, and purified by column chromatography to afford 2.272 g (95%) of the title compound as a pale yellow solid. 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.93 (d, 1H), 8.39 (dd, 1H), 7.61 (dd, 1H), 7.41-7.46 (m, 1H), 4.29 (q, 1H), 3.73 (s, 3H), 1.62 (d, 3H). LCMS (method A): [MH]+=252, tR=5.09 min. (5,7-difluoroquinolin-6-yl)-acetic acid methyl ester was synthesized using the method described in WO2008/144767 p 108 (intermediate 2), followed by the method described for Intermediate 12, step 1 WO2008/144767 p 114.

Workup

  1. customto rise to 0° C.
  2. waitAfter 1 h
  3. customthe reaction was quenched by saturated aqueous NaHCO3 solution
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by column chromatography

Sources & evidence

ORD record
ord-2592a187323c482eb9169c4014477181
Source dataset
uspto-grants-2013_04
Patent number
US08410264B2

Reaction notes

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