Methanesulfonic Acid → 6-Chloro-2-(1-ethyl-propyl)-4-phenyl-quinoline-3-carbonitrile

HRID 1497233Notes

Reaction equation

HRID 1497233 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=O.[CH2:17]([CH:19]([CH2:25][CH3:26])[C:20](=O)[CH2:21][C:22]#[N:23])[CH3:18].CS(O)(=O)=O>C1(C)C=CC=CC=1>[Cl:8][C:5]1[CH:4]=[C:3]2[C:2](=[CH:7][CH:6]=1)[N:1]=[C:20]([CH:19]([CH2:25][CH3:26])[CH2:17][CH3:18])[C:21]([C:22]#[N:23])=[C:9]2[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 6395Methanesulfonic AcidHCID 128702-Amino-5-chlorobenzophenoneHCID 235057484-Ethyl-3-oxohexanenitrile

Product 1

HCID 866830536-Chloro-2-(1-ethyl-propyl)-4-phenyl-quinoline-3-carbonitrileYield 46%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of (2-amino-5-chlorophenyl)(phenyl)methanone (700 mg, 3.02 mmol), 4-ethyl-3-oxo-hexanenitrile (505 mg, 3.63 mmol) and methanesulfonic acid (290 mg, 196 μl, 3.02 mmol) in toluene (40 ml) was stirred for 5 min at room temperature and then heated to reflux using a Dean-Stark-trap to remove water. After 2.5 h the mixture was cooled to room temperature, washed with saturated NaHCO3 solution and water and was evaporated. n-Heptane was added to the remaining residue and the off-white precipitate that formed was filtered off. The precipitate was again dissolved in EtOAc and the solution was washed with saturated NaHCO3 solution and water and was evaporated to yield the title compound (461 mg, 46%) as yellow solid. The filtrate was concentrated and the remaining residue was purified by column chromatography (silica gel, heptane/EtOAc 100:0-0:100) to afford a second batch of the title compound (347 mg, 34%) as yellow solid. MS (ESI): 335.1 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureto reflux
  3. customto remove water
  4. washwashed with saturated NaHCO3 solution and water
  5. customwas evaporated
  6. additionn-Heptane was added to the remaining residue
  7. customthe off-white precipitate that formed
  8. filtrationwas filtered off
  9. dissolutionThe precipitate was again dissolved in EtOAc
  10. washthe solution was washed with saturated NaHCO3 solution and water
  11. customwas evaporated

Sources & evidence

ORD record
ord-4bbb01a9cef34565ab79bd20ae88f471
Source dataset
uspto-grants-2015_12
Patent number
US09199938B2

Reaction notes

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