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

HRID 1412375Notes

Reaction equation

HRID 1412375 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]([F: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[F:30])#[N:29]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 238498Ethyl 3-oxohexanoateHCID 670084324'-(Bromomethyl)-2'-fluorobiphenyl-2-carbonitrile

Product 1

HCID 67009623Ethyl 2-[(2'-cyano-2-fluorobiphenyl-4-yl)methyl]-3-oxohexanoateYield 101.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension (200 mL) of 60% sodium hydride (1.8 g) in tetrahydrofuran was added dropwise a solution (50 mL) of ethyl 3-oxohexanoate (10.9 g) in tetrahydrofuran at 0° C. The mixture was stirred at the same temperature for 30 min, 4′-(bromomethyl)-2′-fluorobiphenyl-2-carbonitrile (10.0 g) was added, and the mixture was stirred at room temperature for 16 hr. The reaction mixture was poured into 1 N hydrochloric acid, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow oil (12.9 g, 100%).

Workup

  1. stirringthe mixture was stirred at room temperature for 16 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe obtained ethyl acetate 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-d4c30d9382cd49389757c8c868cc4bfc
Source dataset
uspto-grants-2014_12
Patent number
US08921379B2

Reaction notes

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