Ethyl cyanoacetate → Ethyl 2-cyano-4-(2,6-difluorophenyl)-4-oxobutanoate

HRID 1012447Notes

Reaction equation

HRID 1012447 reaction equation
[C:1]([CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2].C(N(C(C)C)CC)(C)C.Br[CH2:19][C:20]([C:22]1[C:27]([F:28])=[CH:26][CH:25]=[CH:24][C:23]=1[F:29])=[O:21]>O1CCCC1>[C:1]([CH:3]([CH2:19][C:20]([C:22]1[C:23]([F:29])=[CH:24][CH:25]=[CH:26][C:27]=1[F:28])=[O:21])[C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2]

Participants

5

Reactant 3

HCID 7764Ethyl cyanoacetateHCID 81531DiisopropylethylamineHCID 27782632,6-Difluorophenacyl bromide

Product 1

HCID 66974573Ethyl 2-cyano-4-(2,6-difluorophenyl)-4-oxobutanoateYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of ethyl cyanoacetate (7.24 g) and diisopropylethylamine (19.9 g) in tetrahydrofuran (30 mL) was added dropwise a solution of 2-bromo-1-(2,6-difluorophenyl)ethanone (15.16 g) in tetrahydrofuran (15 mL) at 10-15° C. The mixture was stirred at room temperature for 12 hr. The reaction mixture was filtered, and the obtained filtrate was concentrated under reduced pressure. The residue was dissolved in ethyl acetate, washed successively with water, 1 mol/L hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate=4:1→3:2) to give the title compound as a pale-green oil (yield 13.8 g, 81%).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe obtained filtrate was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed successively with water, 1 mol/L hydrochloric acid 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 (eluent:hexane-ethyl acetate=4:1→3:2)

Sources & evidence

ORD record
ord-3bab1572517c4796b64d1e1cb6e4f4a4
Source dataset
uspto-grants-2011_07
Patent number
US07977488B2

Reaction notes

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