3,3-Diethoxypropiononitrile → 7-Bromoquinoline-3-carbonitrile

HRID 1525927Notes

Reaction equation

HRID 1525927 reaction equation
C(O[CH:4](OCC)[CH2:5][C:6]#[N:7])C.[NH2:11][C:12]1[CH:19]=[C:18]([Br:20])[CH:17]=[CH:16][C:13]=1[CH:14]=O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Br:20][C:18]1[CH:19]=[C:12]2[C:13]([CH:14]=[C:5]([C:6]#[N:7])[CH:4]=[N:11]2)=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 748513,3-DiethoxypropiononitrileHCID 521998p-Toluenesulfonic acid monohydrateHCID 179145982-Amino-4-bromobenzaldehyde

Product 1

HCID 690822957-Bromoquinoline-3-carbonitrileYield 75.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 3,3-diethoxypropanenitrile (1.80 mL, 12.00 mmol), 2-amino-4-bromobenzaldehyde (2 g, 10.00 mmol) and p-toluenesulfonic acid monohydrate (0.380 g, 2.000 mmol) in toluene (30 mL) was heated under reflux using Dean-Stark apparatus for 3 h. The reaction was cooled, evaporated under reduced pressure, and the residue was dissolved in a small amount of DMF, diluted with chloroform, and washed with aq. sodium bicarbonate solution. The aqueous layer was extracted with chloroform, and the combined extracts were washed with brine, dried (Na2SO4), and concentrated in vacuo. Purification by flash chromatography (0-3% methanol in dichloromethane) followed by trituration in diethyl ether provided the title compound (1.75 g, 75%). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.95 (dd, J=8.72, 1.89 Hz, 1 H) 8.08 (d, J=8.84 Hz, 1 H) 8.38 (d, J=2.02 Hz, 1 H) 9.13 (d, J=1.52 Hz, 1 H) 9.21 (d, 1 H).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux
  3. customfor 3 h
  4. temperatureThe reaction was cooled
  5. customevaporated under reduced pressure
  6. dissolutionthe residue was dissolved in a small amount of DMF
  7. additiondiluted with chloroform
  8. washwashed with aq. sodium bicarbonate solution
  9. extractionThe aqueous layer was extracted with chloroform
  10. washthe combined extracts were washed with brine
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated in vacuo
  13. customPurification by flash chromatography (0-3% methanol in dichloromethane)

Sources & evidence

ORD record
ord-9d6b22512f764d21beabcd236cafcee6
Source dataset
uspto-grants-2015_07
Patent number
US09084794B2

Reaction notes

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