4-Chlorobenzylamine → HCID 178510744, compound

HRID 2289926Notes

Reaction equation

HRID 2289926 reaction equation
[C:1]([CH2:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[CH:9][C:8]([C:14]([O:16]CC)=O)=[C:7]2[OH:19])#[N:2].[Cl:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][NH2:26])=[CH:23][CH:22]=1>C(Cl)Cl.CCOCC>[Cl:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][NH:26][C:14]([C:8]2[CH:9]=[N:10][C:11]3[C:6]([C:7]=2[OH:19])=[CH:5][C:4]([CH2:3][C:1]#[N:2])=[CH:13][CH:12]=3)=[O:16])=[CH:23][CH:22]=1

Participants

5

Reactant 2

HCID 660364-ChlorobenzylamineHCID 178469537HCID 178469537, compound

Product 1

HCID 178510744HCID 178510744, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
180 °C

Procedure

A suspension of 4-aminobenyl cyanide (6.61 g) and diethyl ethoxymethylene-malonate (10.1 mL) is heated to 95° C. for 1 hour. The reaction is cooled to room temperature and poured into 50 mL hexanes to wash away impurities. The desired enamine intermediate formed upon cooling and is filtered and collected. In a 3-necked roundbottom connected to a Dean-Stark trap, 75 mL of diphenyl ether is added to the enamine and the solution is heated at 250° C. for 2 hours. The crude product is washed with hot MeOH and dried to yield 3.40 g of ethyl 6-cyanomethyl-4-hydroxyquinoline-3-carboxylate as an orange solid. A mixture of this ester (0.50 g) and p-chlorobenzylamine (3.5 mL) are heated at 180° C. for 1 hour. The reaction is cooled to room temperature and diluted with CH2Cl2 and ether. The solvents are evaporated. The residue is chromatographed on silica, eluting with 3% MeOH in CH2Cl2. Fractions homogenous by TLC are combined, condensed and recrystallized with EtOAc/hexanes to yield 0.162 g of the desired product as a light yellow solid.

Workup

  1. temperatureThe reaction is cooled to room temperature
  2. customThe solvents are evaporated
  3. customThe residue is chromatographed on silica
  4. washeluting with 3% MeOH in CH2Cl2
  5. customcondensed
  6. customrecrystallized with EtOAc/hexanes

Sources & evidence

ORD record
ord-78e7b712b1c5474fa4c3976b4753910b
Source dataset
uspto-grants-2000_07
Patent number
US06093732

Reaction notes

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