Acetic Acid → HCID 67136287, compound

HRID 1921575Notes

Reaction equation

HRID 1921575 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([CH3:12])=[N:7]2.[F:13][C:14]1[C:15]([O:23][CH3:24])=[C:16]([CH:19]=[C:20]([F:22])[CH:21]=1)[CH:17]=O.C(O)(=O)C>C1(C)C=CC=CC=1>[F:13][C:14]1[C:15]([O:23][CH3:24])=[C:16]([CH:17]=[N:1][C:2]2[C:3]3[CH:4]=[CH:5][C:6]([CH3:12])=[N:7][C:8]=3[CH:9]=[CH:10][CH:11]=2)[CH:19]=[C:20]([F:22])[CH:21]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 1486835-Quinolinamine, 2-methyl-HCID 5989943,5-Difluoro-2-methoxybenzaldehyde

Product 1

HCID 67136287HCID 67136287, compoundYield 87.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To 2.0 g (12.6 mmol) 5-amino-2-methylquinolin and 2.2 g (12.6 mmol) 3,5-difluoro-2-methoxybenzaldehyde in 38 ml toluene are added 0.1 ml acetic acid and 5 g molecular sieve. The mixture is heated over 5 hours under reflux and filtrated through a path of cellites after cooling. The solvent is evaporated and the residue is two times azeotrophed with small portions of toluene. 3.43 g of [(3,5-difluoro-2-methoxyphenyl)methylene]-2-methylquinolin-5-amine are obtained as a yellow solid. 1.93 ml (22.3 mmol) 1,1,1-trifluoroepoxypropane in 40 ml THF and 10 ml hexane are cooled to −100° C. and 14 ml of a 1.6 M n-butyl lithium solution in hexane are added over 2 hours while the temperature does not exceed −96° C. 10 Minutes after complete addition 3.44 g (11.2 mmol) [(3,5-difluoro-2-methoxyphenyl)methylene]-2-methylquinolin-5-amine in 50 ml THF are added over 1.5 hours while the temperature temperature does not exceed −95° C. After one hour at −100° C. the reaction mixture is warmed to 0° C. over two hours. The reaction was quenched by addition of saturated ammonium chloride solution. The phases were separated and the aqueous layer was extracted twice with diethyl ether, the combined organic phases washed with brine, dried over sodium sulphate and then evaporated. Flash chromatography on silica gel (isopropanol in hexane 5% to 20%) yields 1.68 g of the desired epoxide.

Workup

  1. temperatureThe mixture is heated over 5 hours
  2. temperatureunder reflux
  3. filtrationfiltrated through a path of cellites
  4. temperatureafter cooling
  5. customThe solvent is evaporated

Sources & evidence

ORD record
ord-274a4367bfa04894b3abf6b93d8f2c10
Source dataset
uspto-grants-2012_05
Patent number
US08173676B2

Reaction notes

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