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

HRID 519875Notes

Reaction equation

HRID 519875 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]([CH3:30])[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[CH3:30])#[N:29]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 238498Ethyl 3-oxohexanoateHCID 670102284'-(Bromomethyl)-2'-methylbiphenyl-2-carbonitrile

Product 1

HCID 67010208Ethyl 2-[(2'-cyano-2-methylbiphenyl-4-yl)methyl]-3-oxohexanoateYield 70.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution (15 mL) of 4′-(hydroxymethyl)-2′-methylbiphenyl-2-carbonitrile (4.12 g) in toluene was added phosphine tribromide (6.00 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 the title compound as a pale-yellow oil (5.08 g, 96%). To a mixture of 60% sodium hydride in oil (1.10 g) and tetrahydrofuran (20 mL) was added dropwise a mixture of ethyl 3-oxohexanoate (5.62 g) in tetrahydrofuran (20 mL) at 0° C., and the mixture was stirred at room temperature for 30 min. Then, 4′-(bromomethyl)-2′-methylbiphenyl-2-carbonitrile (5.08 g) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was poured into 1 M hydrochloric acid (50 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 colorless oil (4.53 g, 70%).

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-58750d9112d543b9b9c6a7ff2be707ba
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

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