Hydrochloric Acid → Ethyl 2-[(3-chloro-2'-cyanobiphenyl-4-yl)methyl]-3-oxohexanoate

HRID 1718913

Reaction equation

HRID 1718913 reaction equation
[H-].[Na+].[C:3]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])(=[O:7])[CH2:4][CH2:5][CH3:6].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][C:17]=1[Cl:30].Cl>O1CCCC1>[Cl:30][C:17]1[CH:18]=[C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[C:28]#[N:29])[CH:20]=[CH:21][C:16]=1[CH2:15][CH:8]([C:3](=[O:7])[CH2:4][CH2:5][CH3:6])[C:9]([O:11][CH2:12][CH3:13])=[O:10]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 238498Ethyl 3-oxohexanoateHCID 269675484'-(Bromomethyl)-3'-chloro-[1,1'-biphenyl]-2-carbonitrile

Product 1

HCID 57460890Ethyl 2-[(3-chloro-2'-cyanobiphenyl-4-yl)methyl]-3-oxohexanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 60% sodium hydride (0.40 g) in tetrahydrofuran (20 mL) was added dropwise a solution of ethyl butyrylacetate (2.13 g) in tetrahydrofuran (10 mL). After stirring for 30 min, 4′-(bromomethyl)-3′-chlorobiphenyl-2-carbonitrile (2.06 g) was added. The mixture was stirred at room temperature for 15 hr, and 1 M hydrochloric acid was added. The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography to give ethyl 2-[(3-chloro-2′-cyanobiphenyl-4-yl)methyl]-3-oxohexanoate. Then, a solution of the obtained ethyl 2-[(3-chloro-2′-cyanobiphenyl-4-yl)methyl]-3-oxohexanoate, ethanimidamide hydrochloride (2.55 g), 28% sodium methoxide (7.80 g) in methanol (50 mL) was stirred overnight. The solvent was evaporated under reduced pressure, and saturated aqueous ammonium chloride solution was added to the residue. The precipitated solid was collected by filtration, and washed with water and diethyl ether to give the title compound (0.64 g, 73%) as a white solid.

Workup

  1. stirringThe mixture was stirred at room temperature for 15 hr
  2. extractionThe mixture was extracted with ethyl acetate
  3. washthe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-24bc887a4f524a3082c868b814b65662
Source dataset
uspto-grants-2010_09
Patent number
US07803940B2

Linked notes

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