Sodium hydride → Ethyl 2-[(2'-cyanobiphenyl-4-yl)methyl]-3-oxohexanoate

HRID 1718421Notes

Reaction equation

HRID 1718421 reaction equation
[H-].[Na+].[O:3]=[C:4]([CH2:11][CH2:12][CH3:13])[CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].Br[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[C:23]([C:28]#[N:29])=[CH:24][CH:25]=[CH:26][CH:27]=2)=[CH:18][CH:17]=1.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[C:28]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[C:19]1[CH:18]=[CH:17][C:16]([CH2:15][CH:5]([C:4](=[O:3])[CH2:11][CH2:12][CH3:13])[C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:21][CH:20]=1)#[N:29]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 238498Ethyl 3-oxohexanoateHCID 15019124'-(Bromomethyl)-2-cyanobiphenyl

Product 1

HCID 10020734Ethyl 2-[(2'-cyanobiphenyl-4-yl)methyl]-3-oxohexanoateYield 100.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of sodium hydride (60% in oil, 19.1 g) in tetrahydrofuran (500 ml) was added a solution of ethyl 3-oxohexanoate (116 g) in tetrahydrofuran (500 ml) dropwise at room temperature. After being stirred at room temperature for 30 min, 4′-(bromomethyl)-biphenyl-2-carbonitrile (100 g) was added to the mixture and the mixture was stirred at room temperature for 15 hr. Ethyl acetate and saturated aqueous ammonium chloride solution were added to the mixture. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were successively washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound as a pale yellow oil (129 g, 100%).

Workup

  1. stirringthe mixture was stirred at room temperature for 15 hr
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washThe combined organic layers were successively washed with water and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-4462bd0269b94f70bc197c3e6dad3541
Source dataset
uspto-grants-2010_09
Patent number
US07803940B2

Reaction notes

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