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

HRID 2090673Notes

Reaction equation

HRID 2090673 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-e39b0fd3a90c4fba8b65c32e10cb6d29
Source dataset
uspto-grants-2013_05
Patent number
US08436187B2

Reaction notes

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