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

HRID 2062812Notes

Reaction equation

HRID 2062812 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)=[C:18]([N+:30]([O-:32])=[O:31])[CH:17]=1.Cl>O1CCCC1>[C:28]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[C:19]1[CH:20]=[CH:21][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:17][C:18]=1[N+:30]([O-:32])=[O:31])#[N:29]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 238498Ethyl 3-oxohexanoateHCID 670096674'-(Bromomethyl)-2'-nitrobiphenyl-2-carbonitrile

Product 1

HCID 67010180Ethyl 2-[(2'-cyano-2-nitrobiphenyl-4-yl)methyl]-3-oxohexanoateYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution (15 mL) of 4′-(hydroxymethyl)-2′-nitrobiphenyl-2-carbonitrile (3.62 g) in toluene was added phosphine tribromide (4.63 g) at room temperature, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated, and the residue was dissolved in ethyl acetate. The obtained ethyl acetate solution was washed with saturated aqueous sodium hydrogen carbonate and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give 4′-(bromomethyl)-2′-nitrobiphenyl-2-carbonitrile as a pale-yellow oil. To a mixture of 60% sodium hydride in oil (0.85 g) and tetrahydrofuran (20 mL) was added dropwise a mixture of ethyl 3-oxohexanoate (4.50 g) in tetrahydrofuran (10 mL) at 0° C., and the mixture was stirred at room temperature for 30 min. Then, the aforementioned 4′-(bromomethyl)-2′-nitrobiphenyl-2-carbonitrile was added, and the mixture was stirred at room temperature overnight. The reaction mixture was poured into 1 M hydrochloric acid (30 mL), and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a yellow oil (4.60 g, 82%).

Workup

  1. additionwas added dropwise
  2. stirringthe mixture was stirred at room temperature overnight
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe ethyl acetate layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0fc74aceb4c14b40ac9fc167a19dc3f2
Source dataset
uspto-grants-2012_10
Patent number
US08283353B2

Reaction notes

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