Diisopropylethylamine → Ethyl 6-fluoroquinoline-3-carboxylate

HRID 1944550Notes

Reaction equation

HRID 1944550 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1Cl)=[CH:13][C:12]([F:17])=[CH:11][CH:10]=2)=[O:5])[CH3:2].C(N(C(C)C)CC)(C)C.[H][H]>C(O)C.[Pd]>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([CH:15]=1)=[CH:13][C:12]([F:17])=[CH:11][CH:10]=2)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 1479088Ethyl 4-chloro-6-fluoroquinoline-3-carboxylateHCID 178418361HCID 178418361, compound2×

Product 1

HCID 53403223Ethyl 6-fluoroquinoline-3-carboxylate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A solution of 4-chloro-6-fluoro-quinoline-3-carboxylic acid ethyl ester (4.2 g, 16.6 mmol) and diisopropylethylamine (8.7 mL, 50 mmol) in ethanol (50 mL) was hydrogenated over 10% palladium on carbon (0.2 g) at 1 atmosphere of hydrogen for 1 day. Additional catalyst (0.3 g) was added and the hydrogenation was continued at 50 psi of hydrogen for 2 hours. The catalyst was removed by filtration. The solvent was evaporated in vacuo, and the residue was partitioned between water and dichloromethane. The organic layer was dried over sodium sulfate. The product was preabsorbed onto silica gel and purified by flash chromatography, using a gradient of ethyl acetate (0% to 30%) in heptanes as the eluant, to give the product as a yellow solid, 2.2 g (60%). MS: m/z 219.9 (MH+).

Workup

  1. customThe catalyst was removed by filtration
  2. customThe solvent was evaporated in vacuo
  3. customthe residue was partitioned between water and dichloromethane
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. customThe product was preabsorbed onto silica gel
  6. custompurified by flash chromatography

Sources & evidence

ORD record
ord-5ee5ad7dc6ef407eba931bde4b617530
Source dataset
uspto-grants-2013_03
Patent number
US08394828B2

Reaction notes

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