Ethyl Acetate → HCID 67408263, compound

HRID 1913413Notes

Reaction equation

HRID 1913413 reaction equation
[C:1]([O:5][C:6](=[O:17])[CH:7]([C:10]1[CH:15]=[CH:14][C:13](Br)=[CH:12][N:11]=1)[C:8]#[N:9])([CH3:4])([CH3:3])[CH3:2].[CH2:18]([Zn]CC)[CH3:19].[Cl-].[NH4+].CCOC(C)=O>C1COCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(Cl)Cl>[C:1]([O:5][C:6](=[O:17])[CH:7]([C:8]#[N:9])[C:10]1[CH:15]=[CH:14][C:13]([CH2:18][CH3:19])=[CH:12][N:11]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 53405506tert-Butyl (5-bromopyridin-2-yl)(cyano)acetateHCID 178418750HCID 178418750, compound

Product 1

HCID 67408263HCID 67408263, compoundYield 43.9%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

The crude (5-bromo-pyridin-2-yl)-cyano-acetic acid tert-butyl ester (20.1 g) was dissolved in anhydrous THF (300 mL) and the dark red solution was cooled in an ice-water bath. After purging in a stream of nitrogen, diethylzinc (88.0 mL, 88.0 mmol, 1M in hexane) was slowly added over 50 minutes. The internal temperature was maintained below 4° C. The catalyst 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride-CH2Cl2 (1:1 complex) (1.61 g, 1.97 mmol) was added and the mixture was heated at 50° C. for 35 minutes. The reaction was cooled in an ice bath and saturated aqueous ammonium chloride solution was added. The mixture was stirred for 10 minutes and EtOAc was added. The mixture was filtered through Celite® with the aid of EtOAc. The filtrate layers were separated and the organic layer was washed with brine and was dried over anhydrous sodium sulfate. The organic solution was concentrated to dryness and the residue was purified by ISCO (Teledyne Isco Inc., Lincoln) column chromatography (EtOAc/heptanes gradient) to give cyano-(5-ethyl-pyridin-2-yl)-acetic acid tert-butyl ester as a dark yellow solid (7.31 g). This material was used directly in the next step.

Workup

  1. temperaturethe dark red solution was cooled in an ice-water bath
  2. additionwas slowly added over 50 minutes
  3. temperatureThe internal temperature was maintained below 4° C
  4. temperatureThe reaction was cooled in an ice bath
  5. filtrationThe mixture was filtered through Celite® with the aid of EtOAc
  6. customThe filtrate layers were separated
  7. washthe organic layer was washed with brine
  8. dry with materialwas dried over anhydrous sodium sulfate
  9. concentrationThe organic solution was concentrated to dryness
  10. customthe residue was purified by ISCO (Teledyne Isco Inc., Lincoln) column chromatography (EtOAc/heptanes gradient)

Sources & evidence

ORD record
ord-70ead66c5fb849b9896823115613c7f9
Source dataset
uspto-grants-2013_12
Patent number
US08609680B2

Reaction notes

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