Diethyl ethylmalonate → 2-(3-Cyano-6-iodo-quinolin-4-yl)-2-ethyl-malonic acid diethyl ester

HRID 1297727Notes

Reaction equation

HRID 1297727 reaction equation
[H-].[K+].[CH2:3]([O:5][C:6](=[O:15])[CH:7]([CH2:13][CH3:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH3:4].Cl[C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([I:27])[CH:25]=2)[N:20]=[CH:19][C:18]=1[C:28]#[N:29]>CCCCCC.O1CCCC1>[CH2:3]([O:5][C:6](=[O:15])[C:7]([C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([I:27])[CH:25]=2)[N:20]=[CH:19][C:18]=1[C:28]#[N:29])([CH2:13][CH3:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH3:4]

Participants

6

Reactant 3

HCID 8610Diethyl ethylmalonateHCID 82127Potassium hydrideHCID 224667694-Chloro-6-iodoquinoline-3-carbonitrile

Product 1

HCID 585858492-(3-Cyano-6-iodo-quinolin-4-yl)-2-ethyl-malonic acid diethyl esterYield 85%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

Potassium hydride (35% oil dispersion, 220 mg, 1.91 mmol) was washed with newly opened hexane for two times under Argon. Then anhydrous tetrahydrofuran (55 mL) was added, followed by addition of 2-ethyl-malonic acid diethyl ester (480 mg, 2.54 mmol). The reaction mixture was stirred at about room temperature for 10 min. Then 4-chloro-6-iodo-quinoline-3-carbonitrile (example 14c, 200 mg, 0.64 mmol) in anhydrous tetrahydrofuran (3 mL) was added to the above reaction mixture, and then reaction continued at room temperature for another 30 min. The reaction was quenched with ice water, and then extracted with ethyl acetate. The organic layers were collected, washed with brain, dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 20% ethyl acetate in hexane in 25 min) afforded 2-(3-cyano-6-iodo-quinolin-4-yl)-2-ethyl-malonic acid diethyl ester (250 mg, 85%) as colorless viscous oil. LC-MS m/e 467 (MH+).

Workup

  1. customreaction
  2. waitcontinued at room temperature for another 30 min
  3. customThe reaction was quenched with ice water
  4. extractionextracted with ethyl acetate
  5. customThe organic layers were collected
  6. washwashed with brain
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d0800e0dccad40b9ae40bbac05b4b6c1
Source dataset
uspto-grants-2007_07
Patent number
US07250515B2

Reaction notes

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