Diethyl Ether → 2-(4-Chloro-2-methoxybenzoyl)cyclopropanecarbonitrile

HRID 561452

Reaction equation

HRID 561452 reaction equation
BrC1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4]C=1OC.[Mg].[C:12]([CH:14]1[CH2:16][CH:15]1[C:17](N(OC)C)=[O:18])#[N:13].[CH2:23]([O:25][CH2:26][CH3:27])C>BrC(Br)C.C1COCC1.C(OCC)(=O)C>[Cl:8][C:6]1[CH:5]=[CH:4][C:27]([C:17]([CH:15]2[CH2:16][CH:14]2[C:12]#[N:13])=[O:18])=[C:26]([O:25][CH3:23])[CH:7]=1

Participants

8

Reactant 4

HCID 3283Diethyl Ether2×HCID 5219352-Bromo-4-chloroanisoleHCID 5462224MagnesiumHCID 583925062-Cyano-N-methoxy-N-methylcyclopropanecarboxamide

Product 1

HCID 583925482-(4-Chloro-2-methoxybenzoyl)cyclopropanecarbonitrile

Reagents, catalysts & solvents 3

HCID 112011,1-DibromoethaneCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 500 mg (2.26 mmol) of 2-bromo-4-chloroanisole in 5 ml of diethyl ether was added dropwise to 57.6 mg (2.37 mmol) of magnesium turnings in 10 ml of diethyl ether, activated by adding a few drops of dibromoethane, and the reaction mixture was heated under reflux overnight. The reaction solution was added dropwise under argon to a solution of 316 mg (2.05 mmol) of the compound from Example 73A in 10 ml of THF, and the reaction mixture was heated under reflux for 2 h. It was diluted with ethyl acetate, and the organic phase was washed with water and saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel (mobile phase: toluene/ethyl acetate 9/1) to result in 278 mg (58% of theory) of the title compound.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureunder reflux overnight
  3. temperaturethe reaction mixture was heated
  4. temperatureunder reflux for 2 h
  5. washthe organic phase was washed with water and saturated aqueous sodium bicarbonate solution
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography on silica gel (mobile phase: toluene/ethyl acetate 9/1)

Sources & evidence

ORD record
ord-1a0de785186246ae8028054f82ac8333
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Linked notes

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