4-Aminophenol → HCID 178469585, compound

HRID 2289931Notes

Reaction equation

HRID 2289931 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C([O:11][CH:12]=[C:13]([C:19](OCC)=O)[C:14]([O:16][CH2:17][CH3:18])=[O:15])C.C1(OC2C=CC=CC=2)C=CC=CC=1>C(O)C>[OH:11][C:12]1[C:7]2[C:2](=[CH:3][CH:4]=[C:5]([OH:8])[CH:6]=2)[N:1]=[CH:19][C:13]=1[C:14]([O:16][CH2:17][CH3:18])=[O:15]

Participants

5

Reactant 3

HCID 4034-AminophenolHCID 6871Diethyl (ethoxymethylene)malonateHCID 7583Diphenyl Ether

Product 1

HCID 178469585HCID 178469585, compoundYield 5.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 4-aminophenol (5.457 g) and diethyl ethoxymethylenemalonate (10.81 g) is heated to 130° C. for 2 h with removal of ethanol by a Dean-Stark trap. The reaction is cooled to room temperature. Diphenyl ether (50 mL) is added and the mixture is heated to 250° C. for 45 min with removal of ethanol by a Dean-Stark trap. The solution is cooled to 80° C. and the resulting solid is collected and washed with hexanes. The solid is suspended in 250 mL MeOH and brought to a boil. The insoluble material is filtered and the filtrate is adsorbed onto silica and chromatographed, eluting with 5% MeOH/CH2Cl2 then with 10% MeOH/CH2Cl2. Fractions homogeneous by TLC are combined and concentrated in vacuo to yield 0.644 g of ethyl 4,6-dihydroxyquinoline-3-carboxylate. A mixture of this ester (0.500 g) and 4-chlorobenzylamine (1.518 g) are heated to 180° C. for 1 h. The solution is cooled to room temperature and diluted with CH2Cl2. The resulting solid is collected and chromatographed on silica, eluting with 3% MeOH/CH2Cl2. Fractions homogeneous by TLC are combined and concentrated in vacuo. The residue is sonicated with CH2Cl2 /hexanes. The resulting solid is collected and dried to afford 0.372 g of the desired product as a white solid.

Workup

  1. temperatureThe solution is cooled to 80° C.
  2. customthe resulting solid is collected
  3. washwashed with hexanes
  4. filtrationThe insoluble material is filtered
  5. customchromatographed
  6. washeluting with 5% MeOH/CH2Cl2
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ff240882011a4a6bb3d4018cb0cf6c6d
Source dataset
uspto-grants-2000_07
Patent number
US06093732

Reaction notes

Loading…